AZD2423 Safety and Tolerability Study in patients with moderate and severe Chronic Obstructive Pulmonary Disease(COPD)

Study identifier:D3320C00002

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 4-week, Double-Blind, Placebo-Controlled, Randomised, Parallel group, Multi-Centre, Phase IIa Study to Investigate the Tolerability and Safety of 100 mg Oral AZD2423 in Patients with Moderate to Severe COPD

Medical condition

Chronic Obstructive Pulmonary Disease

Phase

Phase 2

Healthy volunteers

Study drug

AZD2423, Placebo to AZD2423

Sex

All

Actual Enrollment

Study type

Interventional

Age

40 Years - 80 Years

Date

Study Start Date: 01 Oct 2010

Primary Completion Date: 01 Mar 2011

Study Completion Date: 01 Mar 2011

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Basic Science

Verification:

Verified 01 Oct 2014 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Russe, Bulgaria

Location

Research Site

Sofia, Bulgaria

Location

Research Site

Bratislava, Slovakia

Location

Research Site

Kosice, Slovakia

Location

Research Site

Presov, Slovakia

Location

Research Site

Zilina, Slovakia

Arms	Assigned Interventions
Experimental: AZD2423 AZD2423 Oral Treatment for 28 days	Drug: AZD2423 100 mg oral treatment once daily for 28 days
Placebo Comparator: Placebo Oral treatment for 28 days	Drug: Placebo to AZD2423 Oral treatment once daily for 28 days

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 11 centres in 2 countries: 5 in Bulgaria and 6 in Slovakia. The first patient was enrolled on 09 October 2010 and the last patient last visit was on 08 March 2011.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
None

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Participant Flow: Overall Study

	AZD2423 100 mg	Placebo
STARTED	31	32
COMPLETED	31	32
NOT COMPLETED	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Baseline Measures

	AZD2423 100 mg	Placebo	Total
Number of Participants [units: Participants]	31	32	63
Age Continuous [units: Years] Mean ± Standard Deviation	62.5 ± 7.8	60.6 ± 7.2	61.6 ± 7.5
Gender, Male/Female [units: Participants]
Female	7	9	16
Male	24	23	47

Outcome Measures

1. Primary Outcome Measure: Number of participants with clinically significant changes in laboratory variables other than monocytes [ Time Frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up) ]

Measure Type	Primary
Measure Name	Number of participants with clinically significant changes in laboratory variables other than monocytes
Measure Description	Number of all participants with clinically significant changes in laboratory variables, except monocyte, assessed at all the listed time points
Time Frame	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Number of participants with clinically significant changes in laboratory variables other than monocytes [units: Participants]	0	0

No statistical analysis provided for Number of participants with clinically significant changes in laboratory variables other than monocytes

2. Primary Outcome Measure: Number of participants with clinically significant changes in vital signs [ Time Frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up) ]

Measure Type	Primary
Measure Name	Number of participants with clinically significant changes in vital signs
Measure Description	Number of participants with clinically significant changes in vital signs assessed at all the listed time points
Time Frame	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Number of participants with clinically significant changes in vital signs [units: Participants]	0	0

No statistical analysis provided for Number of participants with clinically significant changes in vital signs

3. Primary Outcome Measure: Number of participants with clinically significant changes in ECG variables [ Time Frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up) ]

Measure Type	Primary
Measure Name	Number of participants with clinically significant changes in ECG variables
Measure Description	Number of participants with clinically significant changes in ECG variables assessed at all the listed time points
Time Frame	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Number of participants with clinically significant changes in ECG variables [units: Participants]	0	0

No statistical analysis provided for Number of participants with clinically significant changes in ECG variables

4. Primary Outcome Measure: Number of participants with clinically significant changes in physical examination [ Time Frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up) ]

Measure Type	Primary
Measure Name	Number of participants with clinically significant changes in physical examination
Measure Description	Number of participants with clinically significant changes in physical examination assessed at all the listed time points
Time Frame	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Number of participants with clinically significant changes in physical examination [units: Participants]	0	0

No statistical analysis provided for Number of participants with clinically significant changes in physical examination

5. Primary Outcome Measure: Monocytes at baseline [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Monocytes at baseline
Measure Description	Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	30	28
Monocytes at baseline [units: 10^9/L] Mean (Standard Deviation)	0.47 (0.136)	0.43 (0.143)

No statistical analysis provided for Monocytes at baseline

6. Primary Outcome Measure: Monocytes at end of treatment [ Time Frame: week 4 ]

Measure Type	Primary
Measure Name	Monocytes at end of treatment
Measure Description	Monocyte count in peripheral blood at end of treatment (4 weeks)
Time Frame	week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	27	29
Monocytes at end of treatment [units: 10^9/L] Mean (Standard Deviation)	0.43 (0.165)	0.55 (0.178)

No statistical analysis provided for Monocytes at end of treatment

7. Primary Outcome Measure: Monocytes at follow-up [ Time Frame: week 5 (follow-up) ]

Measure Type	Primary
Measure Name	Monocytes at follow-up
Measure Description	Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)
Time Frame	week 5 (follow-up)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	27	29
Monocytes at follow-up [units: 10^9/L] Mean (Standard Deviation)	0.50 (0.175)	0.52 (0.196)

No statistical analysis provided for Monocytes at follow-up

8. Secondary Outcome Measure: Morning FEV1 at baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]

Measure Type	Secondary
Measure Name	Morning FEV1 at baseline
Measure Description	Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Morning FEV1 at baseline [units: L] Mean (Standard Deviation)	1.3 (0.41)	1.3 (0.44)

No statistical analysis provided for Morning FEV1 at baseline

9. Secondary Outcome Measure: Morning FEV1 during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	Morning FEV1 during last 7 days of treatment
Measure Description	Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Morning FEV1 during last 7 days of treatment [units: L] Mean (Standard Deviation)	1.3 (0.40)	1.4 (0.52)

No statistical analysis provided for Morning FEV1 during last 7 days of treatment

10. Secondary Outcome Measure: Evening FEV1 at baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]

Measure Type	Secondary
Measure Name	Evening FEV1 at baseline
Measure Description	Measurement conducted by patient in evening.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Evening FEV1 at baseline [units: L] Mean (Standard Deviation)	1.3 (0.43)	1.4 (0.44)

No statistical analysis provided for Evening FEV1 at baseline

11. Secondary Outcome Measure: Evening FEV1 during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	Evening FEV1 during last 7 days of treatment
Measure Description	Measurement conducted by patient in evening.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Evening FEV1 during last 7 days of treatment [units: L] Mean (Standard Deviation)	1.2 (0.37)	1.4 (0.51)

No statistical analysis provided for Evening FEV1 during last 7 days of treatment

12. Secondary Outcome Measure: Morning peak expiratory flow (PEF) at baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]

Measure Type	Secondary
Measure Name	Morning peak expiratory flow (PEF) at baseline
Measure Description	Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Morning peak expiratory flow (PEF) at baseline [units: L/minute] Mean (Standard Deviation)	190.5 (74.73)	185.5 (74.21)

No statistical analysis provided for Morning peak expiratory flow (PEF) at baseline

13. Secondary Outcome Measure: Morning PEF during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	Morning PEF during last 7 days of treatment
Measure Description	Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Morning PEF during last 7 days of treatment [units: L/minute] Mean (Standard Deviation)	190.2 (77.24)	196.4 (83.81)

No statistical analysis provided for Morning PEF during last 7 days of treatment

14. Secondary Outcome Measure: Evening PEF at baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]

Measure Type	Secondary
Measure Name	Evening PEF at baseline
Measure Description	Measurement conducted by patient in evening.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Evening PEF at baseline [units: L/minute] Mean (Standard Deviation)	192.3 (74.27)	196.2 (79.92)

No statistical analysis provided for Evening PEF at baseline

15. Secondary Outcome Measure: Evening PEF during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	Evening PEF during last 7 days of treatment
Measure Description	Measurement conducted by patient in evening.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Evening PEF during last 7 days of treatment [units: L/minute] Mean (Standard Deviation)	191.9 (82.17)	204.7 (87.98)

No statistical analysis provided for Evening PEF during last 7 days of treatment

16. Secondary Outcome Measure: Exacerbations of chronic pulmonary disease tool (EXACT) Total score at baseline [ Time Frame: Average of 7 days of pre-treatment measurements (day -7 to -1) ]

Measure Type	Secondary
Measure Name	Exacerbations of chronic pulmonary disease tool (EXACT) Total score at baseline
Measure Description	The EXACT Tool is a Patient Reported Outcome (PRO) measure; 14 items evaluated on 5- or 6-point scales; total score ranges from 0 to 100 (higher values indicate more severe exacerbation). Baseline is the mean value over the 7 days prior to randomisation.
Time Frame	Average of 7 days of pre-treatment measurements (day -7 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Exacerbations of chronic pulmonary disease tool (EXACT) Total score at baseline [units: Units on scale, 0-100] Mean (Standard Deviation)	44.4 (6.99)	45.7 (8.49)

No statistical analysis provided for Exacerbations of chronic pulmonary disease tool (EXACT) Total score at baseline

17. Secondary Outcome Measure: EXACT Total score during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	EXACT Total score during last 7 days of treatment
Measure Description	The EXACT Tool is a Patient Reported Outcome (PRO) measure; 14 items evaluated on 5- or 6-point scales; total score ranges from 0 to 100 (higher values indicate more severe exacerbation).
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
EXACT Total score during last 7 days of treatment [units: Units on scale, 0-100] Mean (Standard Deviation)	43.8 (7.78)	44.6 (9.84)

No statistical analysis provided for EXACT Total score during last 7 days of treatment

18. Secondary Outcome Measure: Breathlessness, Cough and Sputum Scale (BCSS) (evening) Total score at baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]

Measure Type	Secondary
Measure Name	Breathlessness, Cough and Sputum Scale (BCSS) (evening) Total score at baseline
Measure Description	The BCSS scale includes one question for each of the symptoms of breathlessness, cough, and sputum. The total BCSS score ranges from 0 to 12; higher scores indicate greater symptom severity. The minimally important difference has been defined as a change in total score of greater than 0.3 units. Baseline is mean of 10 days prior to treatment.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Breathlessness, Cough and Sputum Scale (BCSS) (evening) Total score at baseline [units: Units on scale, 0-12] Mean (Standard Deviation)	5.2 (1.40)	5.3 (1.82)

No statistical analysis provided for Breathlessness, Cough and Sputum Scale (BCSS) (evening) Total score at baseline

19. Secondary Outcome Measure: BCSS (evening) Total score during last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	BCSS (evening) Total score during last 7 days of treatment
Measure Description	The BCSS scale includes one question for each of the symptoms of breathlessness, cough, and sputum. The total BCSS score ranges from 0 to 12; higher scores indicate greater symptom severity. The minimally important difference has been defined as a change in total score of greater than 0.3 units.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
BCSS (evening) Total score during last 7 days of treatment [units: Units on scale, 0-12] Mean (Standard Deviation)	5.1 (1.68)	5.1 (2.25)

No statistical analysis provided for BCSS (evening) Total score during last 7 days of treatment

20. Secondary Outcome Measure: Rescue medication use during the last 7 days of treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]

Measure Type	Secondary
Measure Name	Rescue medication use during the last 7 days of treatment
Measure Description	Number of inhalations of short acting β2 agonist (SABA) or short acting muscarinic antagonist (SAMA) per day.
Time Frame	Average of the last 7 days of treatment (week 4)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	30	29
Rescue medication use during the last 7 days of treatment [units: Inhalations] Mean (Full Range)	4.0 (1.0 to 19.3)	3.5 (1.0 to 7.9)

No statistical analysis provided for Rescue medication use during the last 7 days of treatment

21. Secondary Outcome Measure: St George’s Respiratory Questionnaire for COPD (SGRQ) Total score at baseline [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	St George’s Respiratory Questionnaire for COPD (SGRQ) Total score at baseline
Measure Description	The SGRQ-C includes 40 questions in 3 domains: Symptoms (distress due to respiratory symptoms, 7 questions), Activity (disturbance of physical activity, 13 questions), Impacts (overall impact on daily life and well-being, 20 questions). Scores are expressed as a percentage. Baseline is Day 1.
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
St George’s Respiratory Questionnaire for COPD (SGRQ) Total score at baseline [units: Percent of maximum possible score] Mean (Standard Deviation)	55.9 (14.96)	57.0 (19.27)

No statistical analysis provided for St George’s Respiratory Questionnaire for COPD (SGRQ) Total score at baseline

22. Secondary Outcome Measure: SGRQ Total score at end of treatment [ Time Frame: week 4 ]

Measure Type	Secondary
Measure Name	SGRQ Total score at end of treatment
Measure Description	Decrease in score represents improved Quality of Life; increase represents deteriorated Quality of Life. An increase or decrease of 4 or more percent units is judged as the Minimal Clinically Important Difference.
Time Frame	week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
SGRQ Total score at end of treatment [units: Percent of maximum possible score] Mean (Standard Deviation)	52.0 (14.38)	52.9 (18.04)

No statistical analysis provided for SGRQ Total score at end of treatment

23. Secondary Outcome Measure: CCL2 (Chemokine ligand for CCR2b receptor) concentration in plasma at baseline [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	CCL2 (Chemokine ligand for CCR2b receptor) concentration in plasma at baseline
Measure Description	Baseline = Day 1 = Visit 2
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	29	32
CCL2 (Chemokine ligand for CCR2b receptor) concentration in plasma at baseline [units: pg/mL] Geometric Mean (Full Range)	294 (83 to 530)	279 (111 to 635)

No statistical analysis provided for CCL2 (Chemokine ligand for CCR2b receptor) concentration in plasma at baseline

24. Secondary Outcome Measure: CCL2 concentration in plasma at end of treatment [ Time Frame: week 4 ]

Measure Type	Secondary
Measure Name	CCL2 concentration in plasma at end of treatment
Measure Description	End of treatment = 4 weeks = Visit 6
Time Frame	week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
CCL2 concentration in plasma at end of treatment [units: pg/mL] Geometric Mean (Full Range)	1286 (297 to 2410)	272 (97 to 543)

No statistical analysis provided for CCL2 concentration in plasma at end of treatment

25. Secondary Outcome Measure: Serum Amyloid-A (SAA) concentration in plasma at baseline [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	Serum Amyloid-A (SAA) concentration in plasma at baseline
Measure Description	Baseline = Day 1 = Visit 2
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
Serum Amyloid-A (SAA) concentration in plasma at baseline [units: ng/mL] Geometric Mean (Full Range)	5175 (964 to 54100)	4044 (376 to 18600)

No statistical analysis provided for Serum Amyloid-A (SAA) concentration in plasma at baseline

26. Secondary Outcome Measure: SAA concentration in plasma at end of treatment [ Time Frame: week 4 ]

Measure Type	Secondary
Measure Name	SAA concentration in plasma at end of treatment
Measure Description	End of treatment = 4 weeks = Visit 6
Time Frame	week 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	32
SAA concentration in plasma at end of treatment [units: ng/mL] Geometric Mean (Full Range)	6325 (671 to 115000)	4032 (211 to 320000)

No statistical analysis provided for SAA concentration in plasma at end of treatment

27. Secondary Outcome Measure: Areaa under the curve from 0 to 24 hours (AUC 0-24), population pharmacokinetic evaluation of AZD2423 at steady state [ Time Frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 ]

Measure Type	Secondary
Measure Name	Areaa under the curve from 0 to 24 hours (AUC 0-24), population pharmacokinetic evaluation of AZD2423 at steady state
Measure Description	PK-model: 1-compartment population model with first order absorption. AUC was estimated at steady state
Time Frame	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	0
Areaa under the curve from 0 to 24 hours (AUC 0-24), population pharmacokinetic evaluation of AZD2423 at steady state [units: nmol*h/L] Geometric Mean (Full Range)	2780 (1370 to 5410)

No statistical analysis provided for Areaa under the curve from 0 to 24 hours (AUC 0-24), population pharmacokinetic evaluation of AZD2423 at steady state

28. Secondary Outcome Measure: Cmax, population pharmacokinetic evaluation of AZD2423 at steady state [ Time Frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 ]

Measure Type	Secondary
Measure Name	Cmax, population pharmacokinetic evaluation of AZD2423 at steady state
Measure Description	PK-model: 1-compartment population model with first order absorption. Cmaxwas estimated at steady state
Time Frame	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	0
Cmax, population pharmacokinetic evaluation of AZD2423 at steady state [units: nmol/L] Geometric Mean (Full Range)	198 (90.7 to 442)

No statistical analysis provided for Cmax, population pharmacokinetic evaluation of AZD2423 at steady state

29. Secondary Outcome Measure: Time to reach maximum concentration (tmax) population pharmacokinetic evaluation of AZD2423 at steady state [ Time Frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 ]

Measure Type	Secondary
Measure Name	Time to reach maximum concentration (tmax) population pharmacokinetic evaluation of AZD2423 at steady state
Measure Description	PK-model: 1-compartment population model with first order absorption. tmax was estimated at steady state
Time Frame	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	0
Time to reach maximum concentration (tmax) population pharmacokinetic evaluation of AZD2423 at steady state [units: Hours] Median (Full Range)	1.01 (0.82 to 1.06)

No statistical analysis provided for Time to reach maximum concentration (tmax) population pharmacokinetic evaluation of AZD2423 at steady state

30. Secondary Outcome Measure: Apparent volume of distribution at steady state (Vss/F) population pharmacokinetic evaluation of AZD2423 at steady state [ Time Frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution at steady state (Vss/F) population pharmacokinetic evaluation of AZD2423 at steady state
Measure Description	PK-model: 1-compartment population model with first order absorption. (Vss/F) was estimated at steady state
Time Frame	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Measured Values

	AZD2423 100 mg	Placebo
Number of Participants Analyzed [units:participants]	31	0
Apparent volume of distribution at steady state (Vss/F) population pharmacokinetic evaluation of AZD2423 at steady state [units: L] Geometric Mean (Full Range)	1600 (602 to 3650)

No statistical analysis provided for Apparent volume of distribution at steady state (Vss/F) population pharmacokinetic evaluation of AZD2423 at steady state

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Serious Adverse Events

AZD2423 100 mg

Placebo

Total, serious adverse events

# participants affected / at risk

2/31 (6.45%)

0/32 (0.00%)

Cardiac disorders

Atrial Fibrillation¹,^†

# participants affected / at risk

1/31 (3.23%)

0/32 (0.00%)

# events

Cardiac disorders

Atrial Flutter¹,^†

# participants affected / at risk

1/31 (3.23%)

0/32 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD2423 100 mg	Two 50 mg AZD2423 tablets, once daily for 28 days
Placebo	Placebo to match AZD2423 50 mg tablets, once daily for 28 days

Other Adverse Events

AZD2423 100 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

6/31 (19.35%)

2/32 (6.25%)

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

2/31 (6.45%)

1/32 (3.13%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/31 (6.45%)

0/32 (0.00%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/31 (6.45%)

1/32 (3.13%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Anna Malmgren
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

CSR-D3320C00002.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Joanna Marks-Konczalik

AstraZeneca R&D

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site