Trial Outcomes & Findings for Investigation of the Effect of Oral Treatment With 100 mg AZD2423 in Subjects With Mild Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01153321)

NCT ID: NCT01153321

Last Updated: 2015-04-10

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 71 participants
• Primary outcome timeframe: Day 11
• Results posted on: 2015-04-10

Participant Flow

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.

Participant milestones

Measure	AZD2423 Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
Overall Study STARTED	22	22
Overall Study COMPLETED	21	19
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	AZD2423 Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
Overall Study Development of study withdrawal criteria	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily	Total n=44 Participants Total of all reporting groups
Age, Continuous	51.8 Years STANDARD_DEVIATION 7.6 • n=5 Participants	54.1 Years STANDARD_DEVIATION 8.1 • n=7 Participants	53 Years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	13 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Absolute Monocyte Count in BAL Post-LPS Challenge	398 x10^4 cells/mL Standard Error 1.276	514.4 x10^4 cells/mL Standard Error 1.284

SECONDARY outcome

Timeframe: 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. Six patients had missing observations.

Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.

Outcome measures

Measure	AZD2423 n=18 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=15 Participants Placebo to match AZD2423 tablets, once daily
Total Neutrophils in Biopsy Sample (Post-LPS Challenge)	20.7 cells/mm^2 Standard Error 1.218	34.04 cells/mm^2 Standard Error 1.258

SECONDARY outcome

Timeframe: 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. Six patients had missing observations.

Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.

Outcome measures

Measure	AZD2423 n=18 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=15 Participants Placebo to match AZD2423 tablets, once daily
Total Macrophages in Biopsy Sample (Post-LPS Challenge)	28.44 cells/mm^2 Standard Error 1.233	41.17 cells/mm^2 Standard Error 1.274

SECONDARY outcome

Timeframe: 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. Six patients had missing observations.

Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.

Outcome measures

Measure	AZD2423 n=18 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=15 Participants Placebo to match AZD2423 tablets, once daily
CD45+ in Biopsy Sample (Post-LPS Challenge)	200.7 cells/mm^2 Standard Error 1.133	203.2 cells/mm^2 Standard Error 1.156

SECONDARY outcome

Timeframe: 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. Six patients had missing observations.

Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.

Outcome measures

Measure	AZD2423 n=18 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=15 Participants Placebo to match AZD2423 tablets, once daily
CD3+ in Biopsy Sample (Post-LPS Challenge)	71.84 cells/mm^2 Standard Error 1.212	81.1 cells/mm^2 Standard Error 1.249

SECONDARY outcome

Timeframe: 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. Thirteen patients had missing observations.

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).

Outcome measures

Measure	AZD2423 n=14 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=12 Participants Placebo to match AZD2423 tablets, once daily
Biopsy PAS Reaction Grade (Post-LPS Challenge)	2.55 Units on a scale Standard Error 0.415	2.5 Units on a scale Standard Error 0.615

SECONDARY outcome

Timeframe: 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. Thirteen patients had missing observations.

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

Outcome measures

Measure	AZD2423 n=14 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=12 Participants Placebo to match AZD2423 tablets, once daily
Biopsy Epithelium Grade (Post-LPS Challenge)	2.32 Units on a scale Standard Error 0.32	2.29 Units on a scale Standard Error 0.475

SECONDARY outcome

Timeframe: 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. Five patients had missing observations.

Post-LPS challenge eosinophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=18 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=16 Participants Placebo to match AZD2423 tablets, once daily
Eosinophils in BAL (Post-LPS Challenge)	28.15 x10^4 cells/mL Standard Error 1.264	61.35 x10^4 cells/mL Standard Error 1.338

SECONDARY outcome

Timeframe: 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

Post-LPS challenge lymphocyte differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Lymphocytes in BAL (Post-LPS Challenge)	129.7 x10^4 cells/mL Standard Error 1.242	161.7 x10^4 cells/mL Standard Error 1.257

SECONDARY outcome

Timeframe: 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

Post-LPS challenge neutrophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Neutrophils in BAL (Post-LPS Challenge)	2063 x10^4 cells/mL Standard Error 1.3	1890 x10^4 cells/mL Standard Error 1.319

SECONDARY outcome

Timeframe: 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

Post-LPS challenge macrophage differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Macrophages in BAL (Post-LPS Challenge)	771.1 x10^4 cells/mL Standard Deviation 1.181	917.7 x10^4 cells/mL Standard Deviation 1.186

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge TNF α concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
TNF α Concentration in BAL (Post-LPS Challenge)	2.16 pg/mL Standard Error 1.134	3.11 pg/mL Standard Error 1.142

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge CCL2 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
CCL2 Concentration in BAL (Post-LPS Challenge)	82.47 pg/mL Standard Error 1.128	46.25 pg/mL Standard Error 1.136

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge IL-1β concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
IL-1β Concentration in BAL (Post-LPS Challenge)	0.91 pg/mL Standard Error 1.15	1.05 pg/mL Standard Error 1.159

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge IL-6 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
IL-6 Concentration in BAL (Post-LPS Challenge)	13.97 pg/mL Standard Error 1.213	19.76 pg/mL Standard Error 1.226

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge IL 8 concentration in BAL. LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
IL-8 Concentration in BAL (Post-LPS Challenge)	182.5 pg/mL Standard Error 1.114	207.8 pg/mL Standard Error 1.121

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge RANTES concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=18 Participants Placebo to match AZD2423 tablets, once daily
RANTES Concentration in BAL (Post-LPS Challenge)	3.89 pg/mL Standard Error 1.16	4.82 pg/mL Standard Error 1.169

SECONDARY outcome

Timeframe: 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. One patient had missing observations.

Post-LPS challenge SP-D concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=19 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
SP-D Concentration in BAL (Post-LPS Challenge)	637.3 ng/mL Standard Error 1.081	799.1 ng/mL Standard Error 1.079

SECONDARY outcome

Timeframe: Day 10

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

SAA concentration in blood pre-LPS challenge (Day 10).

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
SAA Concentration in Blood (Pre-LPS Challenge)	2312 ng/mL Standard Error 1.168	2510 ng/mL Standard Error 1.173

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
SAA Concentration in Blood (Post-LPS Challenge)	18615 ng/mL Standard Error 1.201	16312 ng/mL Standard Error 1.207

SECONDARY outcome

Timeframe: Day 10

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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
CCL2 Concentration in Blood (Pre-LPS Challenge)	1212 pg/mL Standard Error 1.041	323.4 pg/mL Standard Error 1.042

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
CCL2 Concentration in Blood (Post-LPS Challenge)	1182 pg/mL Standard Error 1.061	292.9 pg/mL Standard Error 1.063

SECONDARY outcome

Timeframe: Day 10

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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-1β Concentration in Blood (Pre-LPS Challenge)	1.26 pg/mL Standard Error 1.055	1.14 pg/mL Standard Error 1.056

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-1β Concentration in Blood (Post-LPS Challenge)	1.12 pg/mL Standard Error 1.017	1.12 pg/mL Standard Error 1.017

SECONDARY outcome

Timeframe: Day 10

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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-6 Concentration in Blood (Pre-LPS Challenge)	2.61 pg/mL Standard Error 1.087	2.55 pg/mL Standard Error 1.09

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-6 Concentration in Blood (Post-LPS Challenge)	4.41 pg/mL Standard Error 1.215	2.87 pg/mL Standard Error 1.221

SECONDARY outcome

Timeframe: Day 10

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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-8 Concentration in Blood (Pre-LPS Challenge)	8.37 pg/mL Standard Error 1.059	9.47 pg/mL Standard Error 1.061

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
IL-8 Concentration in Blood (Post-LPS Challenge)	12.14 pg/mL Standard Error 1.193	8.85 pg/mL Standard Error 1.199

SECONDARY outcome

Timeframe: Day 10

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

TNF-α concentration in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
TNF-α Concentration in Blood (Pre-LPS Challenge)	13.07 pg/mL Standard Error 1.095	12.55 pg/mL Standard Error 1.097

SECONDARY outcome

Timeframe: 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

TNF-α concentration in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
TNF-α Concentration in Blood (Post-LPS Challenge)	12.11 pg/mL Standard Error 1.09	11.19 pg/mL Standard Error 1.092

SECONDARY outcome

Timeframe: Day 10

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

SP-D concentration in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
SP-D Concentration in Blood (Pre-LPS Challenge)	201.8 ng/mL Standard Error 1.043	181.6 ng/mL Standard Error 1.044

SECONDARY outcome

Timeframe: 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

SP-D concentration in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
SP-D Concentration in Blood (Post-LPS Challenge)	198.8 ng/mL Standard Error 1.041	185.6 ng/mL Standard Error 1.042

SECONDARY outcome

Timeframe: Day 10

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. Three patients had missing observations.

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

Outcome measures

Measure	AZD2423 n=19 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=17 Participants Placebo to match AZD2423 tablets, once daily
CC16 Concentration in Blood (Pre-LPS Challenge)	123.2 ng/mL Standard Error 1.034	125.4 ng/mL Standard Error 1.037

SECONDARY outcome

Timeframe: 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. Five patients had missing observations.

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

Outcome measures

Measure	AZD2423 n=19 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=15 Participants Placebo to match AZD2423 tablets, once daily
CC16 Concentration in Blood (Post-LPS Challenge)	113.7 ng/mL Standard Error 1.039	121.6 ng/mL Standard Error 1.044

SECONDARY outcome

Timeframe: day 10

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

Basophils in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Basophils in Blood (Pre-LPS Challenge)	2.87 x10^4 cells/mL Standard Error 1.106	3.06 x10^4 cells/mL Standard Error 1.106

SECONDARY outcome

Timeframe: 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

Basophils in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Basophils in Blood (Post-LPS Challenge)	2.68 x10^4 cells/mL Standard Error 1.145	3.02 x10^4 cells/mL Standard Error 1.15

SECONDARY outcome

Timeframe: Day 10

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

Eosinophils in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Eosinophils in Blood (Pre-LPS Challenge)	17.19 x10^4 cells/mL Standard Error 1.161	17.32 x10^4 cells/mL Standard Error 1.161

SECONDARY outcome

Timeframe: 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

Eosinophils in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Eosinophils in Blood (Post-LPS Challenge)	15.7 x10^4 cells/mL Standard Error 1.092	19.8 x10^4 cells/mL Standard Error 1.092

SECONDARY outcome

Timeframe: Day 10

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

Lymphocytes in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Lymphocytes in Blood (Pre-LPS Challenge)	226.6 x10^4 cells/mL Standard Error 1.035	215.2 x10^4 cells/mL Standard Error 1.035

SECONDARY outcome

Timeframe: 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

Lymphocytes in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Lymphocytes in Blood (Post-LPS Challenge)	215.7 x10^4 cells/mL Standard Error 1.043	198.8 x10^4 cells/mL Standard Error 1.043

SECONDARY outcome

Timeframe: Day 10

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

Monocytes in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Monocytes in Blood (Pre-LPS Challenge)	45.17 x10^4 cells/mL Standard Error 1.13	51.11 x10^4 cells/mL Standard Error 1.13

SECONDARY outcome

Timeframe: 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

Monocytes in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Monocytes in Blood (Post-LPS Challenge)	51.99 x10^4 cells/mL Standard Error 1.053	63.33 x10^4 cells/mL Standard Error 1.053

SECONDARY outcome

Timeframe: Day 10

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

Neutrophils in blood pre-LPS challenge (Day 10)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Neutrophils in Blood (Pre-LPS Challenge)	461.6 x10^4 cells/mL Standard Error 1.055	464.4 x10^4 cells/mL Standard Error 1.055

SECONDARY outcome

Timeframe: 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

Neutrophils in blood post-LPS challenge (Day 11)

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
Neutrophils in Blood (Post-LPS Challenge)	552.4 x10^4 cells/mL Standard Error 1.083	514.7 x10^4 cells/mL Standard Error 1.083

SECONDARY outcome

Timeframe: 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.

Steady state pharmacokinetic (PK) profile measured on Day 10

Outcome measures

Measure	AZD2423 n=21 Participants Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State	228.77 nmol/L Interval 94.3 to 655.0	—

SECONDARY outcome

Timeframe: 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.

Steady state PK profile measured on Day 10

Outcome measures

Measure	AZD2423 n=21 Participants Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
Time to Cmax (Tmax) of AZD2423 at Steady State	0.3 hours Interval 0.3 to 4.0	—

SECONDARY outcome

Timeframe: 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.

Steady state PK profile measured on Day 10

Outcome measures

Measure	AZD2423 n=21 Participants Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
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 Interval 872.7 to 2259.0	—

SECONDARY outcome

Timeframe: 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.

Steady state PK profile measured on Day 10

Outcome measures

Measure	AZD2423 n=21 Participants Two 50 mg AZD2423 tablets, once daily	Placebo Placebo to match AZD2423 tablets, once daily
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 Interval 488.5 to 1182.9	—

SECONDARY outcome

Timeframe: up to 47 days (visit 1 to visit 6)

Outcome measures

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily
Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 47 days (visit 1 to visit 6)

Outcome measures

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily
Number of Participants With Clinically Relevant Changes in Vital Signs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 47 days (visit 1 to visit 6)

Outcome measures

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily
Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 47 days (visit 1 to visit 6)

Outcome measures

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily
Number of Participants With Clinically Relevant Changes in Physical Examination	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 47 days (visit 1 to visit 6)

Outcome measures

Measure	AZD2423 n=22 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=22 Participants Placebo to match AZD2423 tablets, once daily
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)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Post-LPS challenge CC16 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.

Outcome measures

Measure	AZD2423 n=20 Participants Two 50 mg AZD2423 tablets, once daily	Placebo n=19 Participants Placebo to match AZD2423 tablets, once daily
CC16 Concentration in BAL (Post-LPS Challenge)	2256 ng/mL Standard Error 1.132	2589 ng/mL Standard Error 1.136

Adverse Events

AZD2423 100 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD2423 100 mg n=22 participants at risk	Placebo n=22 participants at risk Placebo to match AZD2423 tablets, once daily
Injury, poisoning and procedural complications PROCEDURAL PAIN	0.00% 0/22	4.5% 1/22 • Number of events 1
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	0.00% 0/22	4.5% 1/22 • Number of events 1
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/22	4.5% 1/22 • Number of events 1

Other adverse events

Measure	AZD2423 100 mg n=22 participants at risk	Placebo n=22 participants at risk Placebo to match AZD2423 tablets, once daily
Ear and labyrinth disorders VERTIGO	0.00% 0/22	9.1% 2/22 • Number of events 3
Gastrointestinal disorders DIARRHOEA	13.6% 3/22 • Number of events 3	13.6% 3/22 • Number of events 3
General disorders FATIGUE	0.00% 0/22	9.1% 2/22 • Number of events 2
Injury, poisoning and procedural complications PROCEDURAL PAIN	4.5% 1/22 • Number of events 1	9.1% 2/22 • Number of events 2
Nervous system disorders HEADACHE	9.1% 2/22 • Number of events 2	22.7% 5/22 • Number of events 9
Respiratory, thoracic and mediastinal disorders COUGH	27.3% 6/22 • Number of events 6	13.6% 3/22 • Number of events 3
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	9.1% 2/22 • Number of events 2	18.2% 4/22 • Number of events 4
Respiratory, thoracic and mediastinal disorders VASOMOTOR RHINITIS	13.6% 3/22 • Number of events 3	0.00% 0/22

Additional Information

Anna Malmgren

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Institutions or Investigators were permitted to publish or present the study results from their site (or the overall results), providing the article or presentation was submitted to and approved by AstraZeneca beforehand.
• Publication restrictions are in place

Restriction type: OTHER