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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01153321
First received: June 28, 2010
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

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


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Lung Disease
Drug: AZD2423
Drug: AZD2423 Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Absolute Monocyte Count in BAL Post-LPS Challenge [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Monocyte count in BAL post-LPS challenge (Day 11)


Secondary Outcome Measures:
  • Total Neutrophils in Biopsy Sample (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.

  • Total Macrophages in Biopsy Sample (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.

  • CD45+ in Biopsy Sample (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.

  • Biopsy PAS Reaction Grade (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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).

  • Biopsy Epithelium Grade (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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

  • Eosinophils in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge eosinophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

  • Lymphocytes in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge lymphocyte differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

  • Neutrophils in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge neutrophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

  • Macrophages in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge macrophage differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

  • TNF α Concentration in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge CCL2 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

  • IL-1β Concentration in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge IL-1β concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

  • IL-6 Concentration in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge IL-6 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) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge IL 8 concentration in BAL. LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

  • RANTES Concentration in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge SP-D concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

  • SAA Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    SAA concentration in blood pre-LPS challenge (Day 10).

  • SAA Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    SAA concentration in blood post-LPS challenge (Day 11)

  • CCL2 Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    CCL2 concentration in blood pre-LPS challenge (Day 10)

  • CCL2 Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    CCL2 concentration in blood post-LPS challenge (Day 11).

  • IL-1β Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    IL-1β concentration in blood pre-LPS challenge (Day 10)

  • IL-1β Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    IL-1β concentration in blood post-LPS challenge (Day 11)

  • IL-6 Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    IL-6 concentration in blood pre-LPS challenge (Day 10)

  • IL-6 Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    IL-6 concentration in blood post-LPS challenge (Day 11)

  • IL-8 Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    IL-8 concentration in blood pre-LPS challenge (Day 10)

  • IL-8 Concentration in Blood (Post-LPS Challenge) [ Time Frame: day 11 ] [ Designated as safety issue: No ]
    IL-8 concentration in blood post-LPS challenge (Day 11)

  • TNF-α Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    TNF-α concentration in blood pre-LPS challenge (Day 10)

  • TNF-α Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    TNF-α concentration in blood post-LPS challenge (Day 11)

  • SP-D Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    SP-D concentration in blood pre-LPS challenge (Day 10)

  • SP-D Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    SP-D concentration in blood post-LPS challenge (Day 11)

  • CC16 Concentration in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    CC16 concentration in blood pre-LPS challenge (Day 10)

  • CC16 Concentration in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    CC16 concentration in blood post-LPS challenge (Day 11)

  • Basophils in Blood (Pre-LPS Challenge) [ Time Frame: day 10 ] [ Designated as safety issue: No ]
    Basophils in blood pre-LPS challenge (Day 10)

  • Basophils in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Basophils in blood post-LPS challenge (Day 11)

  • Eosinophils in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Eosinophils in blood pre-LPS challenge (Day 10)

  • Eosinophils in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Eosinophils in blood post-LPS challenge (Day 11)

  • Lymphocytes in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Lymphocytes in blood pre-LPS challenge (Day 10)

  • Lymphocytes in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Lymphocytes in blood post-LPS challenge (Day 11)

  • Monocytes in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Monocytes in blood pre-LPS challenge (Day 10)

  • Monocytes in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Monocytes in blood post-LPS challenge (Day 11)

  • Neutrophils in Blood (Pre-LPS Challenge) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Neutrophils in blood pre-LPS challenge (Day 10)

  • Neutrophils in Blood (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Neutrophils in blood post-LPS challenge (Day 11)

  • Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State [ Time Frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose ] [ Designated as safety issue: No ]
    Steady state pharmacokinetic (PK) profile measured on Day 10

  • Time to Cmax (Tmax) of AZD2423 at Steady State [ Time Frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose ] [ Designated as safety issue: No ]
    Steady state PK profile measured on Day 10

  • Area Under the Plasma Concentration-time Curve From Zero to 24 Hours (AUC(0-24)) of AZD2423 at Steady State [ Time Frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose ] [ Designated as safety issue: No ]
    Steady state PK profile measured on Day 10

  • Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes [ Time Frame: up to 47 days (visit 1 to visit 6) ] [ Designated as safety issue: No ]
  • Number of Participants With Clinically Relevant Changes in Vital Signs [ Time Frame: up to 47 days (visit 1 to visit 6) ] [ Designated as safety issue: No ]
  • Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables [ Time Frame: up to 47 days (visit 1 to visit 6) ] [ Designated as safety issue: No ]
  • Number of Participants With Clinically Relevant Changes in Physical Examination [ Time Frame: up to 47 days (visit 1 to visit 6) ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: up to 47 days (visit 1 to visit 6) ] [ Designated as safety issue: No ]
  • CC16 Concentration in BAL (Post-LPS Challenge) [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Post-LPS challenge CC16 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.


Enrollment: 71
Study Start Date: October 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Oral treatment
Drug: AZD2423
100mg Oral dose od
Placebo Comparator: 2
Oral treatment
Drug: AZD2423 Placebo
Oral dose od

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01153321

Locations
Germany
Research Site
Hannover, Germany
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bengt Larsson AstraZeneca R&D
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01153321     History of Changes
Other Study ID Numbers: D3320C00001, 2010-020141-26
Study First Received: June 28, 2010
Results First Received: July 15, 2013
Last Updated: October 17, 2014
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by AstraZeneca:
Respiratory disease
chronic obstructive pulmonary disease

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014