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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01153321

Enrollment

Registered

2010-06-30

Start date

2010-10-31

Completion date

2011-07-31

Last updated

2015-04-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease, Lung Disease

Keywords

Respiratory disease, chronic obstructive pulmonary disease

Brief summary

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

Interventions

DRUGAZD2423

100mg Oral dose od

DRUGAZD2423 Placebo

Oral dose od

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Absolute Monocyte Count in BAL Post-LPS Challenge	Day 11	Monocyte count in BAL post-LPS challenge (Day 11)

Secondary

Measure	Time frame	Description
TNF-α Concentration in Blood (Post-LPS Challenge)	Day 11	TNF-α concentration in blood post-LPS challenge (Day 11)
SP-D Concentration in Blood (Pre-LPS Challenge)	Day 10	SP-D concentration in blood pre-LPS challenge (Day 10)
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.
Total Neutrophils in Biopsy Sample (Post-LPS Challenge)	Day 11	Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.
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.
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 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).
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
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.
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.
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.
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.
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.
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.
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.
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.
SAA Concentration in Blood (Pre-LPS Challenge)	Day 10	SAA concentration in blood pre-LPS challenge (Day 10).
SAA Concentration in Blood (Post-LPS Challenge)	Day 11	SAA concentration in blood post-LPS challenge (Day 11)
CCL2 Concentration in Blood (Pre-LPS Challenge)	Day 10	CCL2 concentration in blood pre-LPS challenge (Day 10)
CCL2 Concentration in Blood (Post-LPS Challenge)	Day 11	CCL2 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 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)
IL-8 Concentration in Blood (Pre-LPS Challenge)	Day 10	IL-8 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)
SP-D Concentration in Blood (Post-LPS Challenge)	Day 11	SP-D concentration in blood post-LPS challenge (Day 11)
CC16 Concentration in Blood (Pre-LPS Challenge)	Day 10	CC16 concentration in blood pre-LPS challenge (Day 10)
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)
Basophils in Blood (Post-LPS Challenge)	Day 11	Basophils in blood post-LPS challenge (Day 11)
Eosinophils in Blood (Pre-LPS Challenge)	Day 10	Eosinophils in blood pre-LPS challenge (Day 10)
Eosinophils in Blood (Post-LPS Challenge)	Day 11	Eosinophils in blood post-LPS challenge (Day 11)
Lymphocytes in Blood (Pre-LPS Challenge)	Day 10	Lymphocytes in blood pre-LPS challenge (Day 10)
Lymphocytes in Blood (Post-LPS Challenge)	Day 11	Lymphocytes 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)
Neutrophils in Blood (Pre-LPS Challenge)	Day 10	Neutrophils 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
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
TNF-α Concentration in Blood (Pre-LPS Challenge)	Day 10	TNF-α concentration in blood pre-LPS challenge (Day 10)
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)	Day 11	Post-LPS challenge CC16 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes	up to 47 days (visit 1 to visit 6)	—

Countries

Germany

Participant flow

Recruitment details

This was a single centre study conducted at a medical research centre in Germany. The first patient was enrolled on 01 October 2010 and the last patient last visit was on 28 July 2011. A total of 71 subjects were enrolled to get 44 subjects that fulfilled the inclusion criterions.

Participants by arm

Arm	Count
AZD2423 Two 50 mg AZD2423 tablets, once daily	22
Placebo Placebo to match AZD2423 tablets, once daily	22
Total	44

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Development of study withdrawal criteria	0	1
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	AZD2423	Placebo	Total
Age, Continuous	51.8 Years STANDARD_DEVIATION 7.6	54.1 Years STANDARD_DEVIATION 8.1	53 Years STANDARD_DEVIATION 7.9
Sex: Female, Male Female	2 Participants	9 Participants	11 Participants
Sex: Female, Male Male	20 Participants	13 Participants	33 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	10 / 22	15 / 22
serious Total, serious adverse events	0 / 22	3 / 22

Outcome results

Primary

Absolute Monocyte Count in BAL Post-LPS Challenge

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

Time frame: Day 11

Population: Thirty-nine patients were included in the efficacy analysis set. Five patients were excluded because they did not have sufficient data to be included in the primary outcome analysis. Four discontinued and one did not complete LPS challenge

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Absolute Monocyte Count in BAL Post-LPS Challenge	398 x10^4 cells/mL	Standard Error 1.276
Placebo	Absolute Monocyte Count in BAL Post-LPS Challenge	514.4 x10^4 cells/mL	Standard Error 1.284

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

Time frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

Population: All 22 patients who received AZD2423 provided at least one plasma sample and were included in the PK analysis although only 21 patients were included in the evaluation of PK at day 10, one patient had been discontinued due to an AE.

Arm	Measure	Value (GEOMETRIC_MEAN)
AZD2423	Area Under the Plasma Concentration-time Curve From Zero to 24 Hours (AUC(0-24)) of AZD2423 at Steady State	1454.14 nmol*h/L

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

Time frame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)
AZD2423	Area Under the Plasma Concentration-time Curve From Zero to 8 Hours (AUC(0-8)) of AZD2423 at Steady State	801.25 nmol*h/L

Secondary

Basophils in Blood (Post-LPS Challenge)

Basophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Basophils in Blood (Post-LPS Challenge)	2.68 x10^4 cells/mL	Standard Error 1.145
Placebo	Basophils in Blood (Post-LPS Challenge)	3.02 x10^4 cells/mL	Standard Error 1.15

Secondary

Basophils in Blood (Pre-LPS Challenge)

Basophils in blood pre-LPS challenge (Day 10)

Time frame: day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Basophils in Blood (Pre-LPS Challenge)	2.87 x10^4 cells/mL	Standard Error 1.106
Placebo	Basophils in Blood (Pre-LPS Challenge)	3.06 x10^4 cells/mL	Standard Error 1.106

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

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Biopsy Epithelium Grade (Post-LPS Challenge)	2.32 Units on a scale	Standard Error 0.32
Placebo	Biopsy Epithelium Grade (Post-LPS Challenge)	2.29 Units on a scale	Standard Error 0.475

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).

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Biopsy PAS Reaction Grade (Post-LPS Challenge)	2.55 Units on a scale	Standard Error 0.415
Placebo	Biopsy PAS Reaction Grade (Post-LPS Challenge)	2.5 Units on a scale	Standard Error 0.615

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CC16 Concentration in BAL (Post-LPS Challenge)	2256 ng/mL	Standard Error 1.132
Placebo	CC16 Concentration in BAL (Post-LPS Challenge)	2589 ng/mL	Standard Error 1.136

Secondary

CC16 Concentration in Blood (Post-LPS Challenge)

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

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CC16 Concentration in Blood (Post-LPS Challenge)	113.7 ng/mL	Standard Error 1.039
Placebo	CC16 Concentration in Blood (Post-LPS Challenge)	121.6 ng/mL	Standard Error 1.044

Secondary

CC16 Concentration in Blood (Pre-LPS Challenge)

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

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CC16 Concentration in Blood (Pre-LPS Challenge)	123.2 ng/mL	Standard Error 1.034
Placebo	CC16 Concentration in Blood (Pre-LPS Challenge)	125.4 ng/mL	Standard Error 1.037

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CCL2 Concentration in BAL (Post-LPS Challenge)	82.47 pg/mL	Standard Error 1.128
Placebo	CCL2 Concentration in BAL (Post-LPS Challenge)	46.25 pg/mL	Standard Error 1.136

Secondary

CCL2 Concentration in Blood (Post-LPS Challenge)

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

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CCL2 Concentration in Blood (Post-LPS Challenge)	1182 pg/mL	Standard Error 1.061
Placebo	CCL2 Concentration in Blood (Post-LPS Challenge)	292.9 pg/mL	Standard Error 1.063

Secondary

CCL2 Concentration in Blood (Pre-LPS Challenge)

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

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CCL2 Concentration in Blood (Pre-LPS Challenge)	1212 pg/mL	Standard Error 1.041
Placebo	CCL2 Concentration in Blood (Pre-LPS Challenge)	323.4 pg/mL	Standard Error 1.042

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CD3+ in Biopsy Sample (Post-LPS Challenge)	71.84 cells/mm^2	Standard Error 1.212
Placebo	CD3+ in Biopsy Sample (Post-LPS Challenge)	81.1 cells/mm^2	Standard Error 1.249

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	CD45+ in Biopsy Sample (Post-LPS Challenge)	200.7 cells/mm^2	Standard Error 1.133
Placebo	CD45+ in Biopsy Sample (Post-LPS Challenge)	203.2 cells/mm^2	Standard Error 1.156

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Eosinophils in BAL (Post-LPS Challenge)	28.15 x10^4 cells/mL	Standard Error 1.264
Placebo	Eosinophils in BAL (Post-LPS Challenge)	61.35 x10^4 cells/mL	Standard Error 1.338

Secondary

Eosinophils in Blood (Post-LPS Challenge)

Eosinophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Eosinophils in Blood (Post-LPS Challenge)	15.7 x10^4 cells/mL	Standard Error 1.092
Placebo	Eosinophils in Blood (Post-LPS Challenge)	19.8 x10^4 cells/mL	Standard Error 1.092

Secondary

Eosinophils in Blood (Pre-LPS Challenge)

Eosinophils in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Eosinophils in Blood (Pre-LPS Challenge)	17.19 x10^4 cells/mL	Standard Error 1.161
Placebo	Eosinophils in Blood (Pre-LPS Challenge)	17.32 x10^4 cells/mL	Standard Error 1.161

Secondary

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-1β Concentration in BAL (Post-LPS Challenge)	0.91 pg/mL	Standard Error 1.15
Placebo	IL-1β Concentration in BAL (Post-LPS Challenge)	1.05 pg/mL	Standard Error 1.159

Secondary

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

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

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-1β Concentration in Blood (Post-LPS Challenge)	1.12 pg/mL	Standard Error 1.017
Placebo	IL-1β Concentration in Blood (Post-LPS Challenge)	1.12 pg/mL	Standard Error 1.017

Secondary

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

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

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-1β Concentration in Blood (Pre-LPS Challenge)	1.26 pg/mL	Standard Error 1.055
Placebo	IL-1β Concentration in Blood (Pre-LPS Challenge)	1.14 pg/mL	Standard Error 1.056

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-6 Concentration in BAL (Post-LPS Challenge)	13.97 pg/mL	Standard Error 1.213
Placebo	IL-6 Concentration in BAL (Post-LPS Challenge)	19.76 pg/mL	Standard Error 1.226

Secondary

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

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

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-6 Concentration in Blood (Post-LPS Challenge)	4.41 pg/mL	Standard Error 1.215
Placebo	IL-6 Concentration in Blood (Post-LPS Challenge)	2.87 pg/mL	Standard Error 1.221

Secondary

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

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

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-6 Concentration in Blood (Pre-LPS Challenge)	2.61 pg/mL	Standard Error 1.087
Placebo	IL-6 Concentration in Blood (Pre-LPS Challenge)	2.55 pg/mL	Standard Error 1.09

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-8 Concentration in BAL (Post-LPS Challenge)	182.5 pg/mL	Standard Error 1.114
Placebo	IL-8 Concentration in BAL (Post-LPS Challenge)	207.8 pg/mL	Standard Error 1.121

Secondary

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

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

Time frame: day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-8 Concentration in Blood (Post-LPS Challenge)	12.14 pg/mL	Standard Error 1.193
Placebo	IL-8 Concentration in Blood (Post-LPS Challenge)	8.85 pg/mL	Standard Error 1.199

Secondary

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

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

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	IL-8 Concentration in Blood (Pre-LPS Challenge)	8.37 pg/mL	Standard Error 1.059
Placebo	IL-8 Concentration in Blood (Pre-LPS Challenge)	9.47 pg/mL	Standard Error 1.061

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Lymphocytes in BAL (Post-LPS Challenge)	129.7 x10^4 cells/mL	Standard Error 1.242
Placebo	Lymphocytes in BAL (Post-LPS Challenge)	161.7 x10^4 cells/mL	Standard Error 1.257

Secondary

Lymphocytes in Blood (Post-LPS Challenge)

Lymphocytes in blood post-LPS challenge (Day 11)

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Lymphocytes in Blood (Post-LPS Challenge)	215.7 x10^4 cells/mL	Standard Error 1.043
Placebo	Lymphocytes in Blood (Post-LPS Challenge)	198.8 x10^4 cells/mL	Standard Error 1.043

Secondary

Lymphocytes in Blood (Pre-LPS Challenge)

Lymphocytes in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Lymphocytes in Blood (Pre-LPS Challenge)	226.6 x10^4 cells/mL	Standard Error 1.035
Placebo	Lymphocytes in Blood (Pre-LPS Challenge)	215.2 x10^4 cells/mL	Standard Error 1.035

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Macrophages in BAL (Post-LPS Challenge)	771.1 x10^4 cells/mL	Standard Deviation 1.181
Placebo	Macrophages in BAL (Post-LPS Challenge)	917.7 x10^4 cells/mL	Standard Deviation 1.186

Secondary

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

Arm	Measure	Value (GEOMETRIC_MEAN)
AZD2423	Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State	228.77 nmol/L

Secondary

Monocytes in Blood (Post-LPS Challenge)

Monocytes in blood post-LPS challenge (Day 11)

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Monocytes in Blood (Post-LPS Challenge)	51.99 x10^4 cells/mL	Standard Error 1.053
Placebo	Monocytes in Blood (Post-LPS Challenge)	63.33 x10^4 cells/mL	Standard Error 1.053

Secondary

Monocytes in Blood (Pre-LPS Challenge)

Monocytes in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Monocytes in Blood (Pre-LPS Challenge)	45.17 x10^4 cells/mL	Standard Error 1.13
Placebo	Monocytes in Blood (Pre-LPS Challenge)	51.11 x10^4 cells/mL	Standard Error 1.13

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.

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Neutrophils in BAL (Post-LPS Challenge)	2063 x10^4 cells/mL	Standard Error 1.3
Placebo	Neutrophils in BAL (Post-LPS Challenge)	1890 x10^4 cells/mL	Standard Error 1.319

Secondary

Neutrophils in Blood (Post-LPS Challenge)

Neutrophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Neutrophils in Blood (Post-LPS Challenge)	552.4 x10^4 cells/mL	Standard Error 1.083
Placebo	Neutrophils in Blood (Post-LPS Challenge)	514.7 x10^4 cells/mL	Standard Error 1.083

Secondary

Neutrophils in Blood (Pre-LPS Challenge)

Neutrophils in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AZD2423	Neutrophils in Blood (Pre-LPS Challenge)	461.6 x10^4 cells/mL	Standard Error 1.055
Placebo	Neutrophils in Blood (Pre-LPS Challenge)	464.4 x10^4 cells/mL	Standard Error 1.055

Secondary