AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01215279
• Collaborator: (none)
• Enrollment: 63
• Locations: 6
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 10.5
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of the study is to investigate the tolerability and safety of AZD2423 in Patients with chronic obstructive pulmonary disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease; Lung Disease	Drug: AZD2423; Drug: Placebo to AZD2423	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• 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
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes [Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)]

   Number of all participants with clinically significant changes in laboratory variables, except monocyte, assessed at all the listed time points

2. Number of Participants With Clinically Significant Changes in Vital Signs [Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)]

   Number of participants with clinically significant changes in vital signs assessed at all the listed time points

3. Number of Participants With Clinically Significant Changes in ECG Variables [Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)]

   Number of participants with clinically significant changes in ECG variables assessed at all the listed time points

4. Number of Participants With Clinically Significant Changes in Physical Examination [Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)]

   Number of participants with clinically significant changes in physical examination assessed at all the listed time points

5. Monocytes at Baseline [Day 1]

   Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)

6. Monocytes at End of Treatment [week 4]

   Monocyte count in peripheral blood at end of treatment (4 weeks)

7. Monocytes at Follow-up [week 5 (follow-up)]

   Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)

Secondary Outcome Measures

1. Morning FEV1 at Baseline [Average of 10 days of pre-treatment measurements (day -10 to -1)]

   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.

2. Morning FEV1 During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

   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.

3. Evening FEV1 at Baseline [Average of 10 days of pre-treatment measurements (day -10 to -1)]

   Measurement conducted by patient in evening.

4. Evening FEV1 During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

   Measurement conducted by patient in evening.

5. Morning Peak Expiratory Flow (PEF) at Baseline [Average of 10 days of pre-treatment measurements (day -10 to -1)]

   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.

6. Morning PEF During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

   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.

7. Evening PEF at Baseline [Average of 10 days of pre-treatment measurements (day -10 to -1)]

   Measurement conducted by patient in evening.

8. Evening PEF During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

   Measurement conducted by patient in evening.

9. Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline [Average of 7 days of pre-treatment measurements (day -7 to -1)]

   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.

10. EXACT Total Score During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

    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).

11. Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline [Average of 10 days of pre-treatment measurements (day -10 to -1)]

    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.

12. BCSS (Evening) Total Score During Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

    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.

13. Rescue Medication Use During the Last 7 Days of Treatment [Average of the last 7 days of treatment (week 4)]

    Number of inhalations of short acting β2 agonist (SABA) or short acting muscarinic antagonist (SAMA) per day.

14. St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline [Day 1]

    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.

15. SGRQ Total Score at End of Treatment [week 4]

    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.

16. CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline [Day 1]

    Baseline = Day 1 = Visit 2

17. CCL2 Concentration in Plasma at End of Treatment [week 4]

    End of treatment = 4 weeks = Visit 6

18. Serum Amyloid-A (SAA) Concentration in Plasma at Baseline [Day 1]

    Baseline = Day 1 = Visit 2

19. SAA Concentration in Plasma at End of Treatment [week 4]

    End of treatment = 4 weeks = Visit 6

20. Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State [2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4]

    PK-model: 1-compartment population model with first order absorption. AUC was estimated at steady state

21. Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State [2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4]

    PK-model: 1-compartment population model with first order absorption. Cmaxwas estimated at steady state

22. Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State [2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4]

    PK-model: 1-compartment population model with first order absorption. tmax was estimated at steady state

23. Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State [2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4]

    PK-model: 1-compartment population model with first order absorption. (Vss/F) was estimated at steady state

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female of non-child bearing potential. Only women of non-child bearing potential are included in the study i.e. women who are permanently or surgically sterilised or post menopausal.

• Between 40 and 80 years of age at Visit 1

• Clinical diagnosis of COPD (GOLD stage 2 or 3)

• FEV1/FVC <70% and FEV1 between 30 and 80% of the predicted normal post-bronchodilator (GOLD stage 2 or 3)

• Current or ex-smokers

Exclusion Criteria:

• Any clinically significant disease or disorder (including history of abnormal immune function) which, in the opinion of the Investigator, may either put the subject at risk or influence the way the drug works

• Any lung disease other than COPD, recent respiratory infections which have not resolved fully, active tuberculosis or at risk of reactivation of tuberculosis.

• Any 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 to take part or influence the results of the study

• Immunisation with a live vaccine within 3 months or other vaccination within 30 days before planned start of treatment

• Worsening of COPD symptoms within 4 weeks prior to start of study needing hospitalisation, oral steroids or antibiotics.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Russe		Bulgaria
2	Research Site	Sofia		Bulgaria
3	Research Site	Bratislava		Slovakia
4	Research Site	Kosice		Slovakia
5	Research Site	Presov		Slovakia
6	Research Site	Zilina		Slovakia

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Joanna Marks-Konczalik, MD, PhD, AstraZeneca R&D

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D3320C00002.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01215279
• Other Study ID Numbers: D3320C00002
• First Posted: Oct 6, 2010
• Last Update Posted: Oct 23, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by AstraZeneca: Respiratory disease; Chronic Obstructive Pulmonary Disease
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Period Title: Overall Study
STARTED	31	32
COMPLETED	31	32
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AZD2423 100 mg	Placebo	Total
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days	Total of all reporting groups
Overall Participants	31	32	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.5 (7.8)	60.6 (7.2)	61.6 (7.5)
Sex: Female, Male (Count of Participants)
Female	7 22.6%	9 28.1%	16 25.4%
Male	24 77.4%	23 71.9%	47 74.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Number [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Vital Signs
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Number [Participants]	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in ECG Variables
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Number [Participants]	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Physical Examination
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Number [Participants]	0 0%	0 0%

5. Primary Outcome

Title	Monocytes at Baseline
Description	Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	30	28
Mean (Standard Deviation) [10^9/L]	0.47 (0.136)	0.43 (0.143)

6. Primary Outcome

Title	Monocytes at End of Treatment
Description	Monocyte count in peripheral blood at end of treatment (4 weeks)
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	27	29
Mean (Standard Deviation) [10^9/L]	0.43 (0.165)	0.55 (0.178)

7. Primary Outcome

Title	Monocytes at Follow-up
Description	Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)
Time Frame	week 5 (follow-up)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	27	29
Mean (Standard Deviation) [10^9/L]	0.50 (0.175)	0.52 (0.196)

8. Secondary Outcome

Title	Morning FEV1 at Baseline
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L]	1.3 (0.41)	1.3 (0.44)

9. Secondary Outcome

Title	Morning FEV1 During Last 7 Days of Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L]	1.3 (0.40)	1.4 (0.52)

10. Secondary Outcome

Title	Evening FEV1 at Baseline
Description	Measurement conducted by patient in evening.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L]	1.3 (0.43)	1.4 (0.44)

11. Secondary Outcome

Title	Evening FEV1 During Last 7 Days of Treatment
Description	Measurement conducted by patient in evening.
Time Frame	Average of the last 7 days of treatment (week 4)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L]	1.2 (0.37)	1.4 (0.51)

12. Secondary Outcome

Title	Morning Peak Expiratory Flow (PEF) at Baseline
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L/minute]	190.5 (74.73)	185.5 (74.21)

13. Secondary Outcome

Title	Morning PEF During Last 7 Days of Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L/minute]	190.2 (77.24)	196.4 (83.81)

14. Secondary Outcome

Title	Evening PEF at Baseline
Description	Measurement conducted by patient in evening.
Time Frame	Average of 10 days of pre-treatment measurements (day -10 to -1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L/minute]	192.3 (74.27)	196.2 (79.92)

15. Secondary Outcome

Title	Evening PEF During Last 7 Days of Treatment
Description	Measurement conducted by patient in evening.
Time Frame	Average of the last 7 days of treatment (week 4)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [L/minute]	191.9 (82.17)	204.7 (87.98)

16. Secondary Outcome

Title	Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Units on scale, 0-100]	44.4 (6.99)	45.7 (8.49)

17. Secondary Outcome

Title	EXACT Total Score During Last 7 Days of Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Units on scale, 0-100]	43.8 (7.78)	44.6 (9.84)

18. Secondary Outcome

Title	Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Units on scale, 0-12]	5.2 (1.40)	5.3 (1.82)

19. Secondary Outcome

Title	BCSS (Evening) Total Score During Last 7 Days of Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Units on scale, 0-12]	5.1 (1.68)	5.1 (2.25)

20. Secondary Outcome

Title	Rescue Medication Use During the Last 7 Days of Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	30	29
Mean (Full Range) [Inhalations]	4.0 (1.0)	3.5 (1.0)

21. Secondary Outcome

Title	St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Percent of maximum possible score]	55.9 (14.96)	57.0 (19.27)

22. Secondary Outcome

Title	SGRQ Total Score at End of Treatment
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Mean (Standard Deviation) [Percent of maximum possible score]	52.0 (14.38)	52.9 (18.04)

23. Secondary Outcome

Title	CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline
Description	Baseline = Day 1 = Visit 2
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	29	32
Geometric Mean (Full Range) [pg/mL]	294	279

24. Secondary Outcome

Title	CCL2 Concentration in Plasma at End of Treatment
Description	End of treatment = 4 weeks = Visit 6
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Geometric Mean (Full Range) [pg/mL]	1286	272

25. Secondary Outcome

Title	Serum Amyloid-A (SAA) Concentration in Plasma at Baseline
Description	Baseline = Day 1 = Visit 2
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Geometric Mean (Full Range) [ng/mL]	5175	4044

26. Secondary Outcome

Title	SAA Concentration in Plasma at End of Treatment
Description	End of treatment = 4 weeks = Visit 6
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	32
Geometric Mean (Full Range) [ng/mL]	6325	4032

27. Secondary Outcome

Title	Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	0
Geometric Mean (Full Range) [nmol*h/L]	2780

28. Secondary Outcome

Title	Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	0
Geometric Mean (Full Range) [nmol/L]	198

29. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	0
Median (Full Range) [Hours]	1.01

30. Secondary Outcome

Title	Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD2423 100 mg	Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days	Placebo to match AZD2423 50 mg tablets, once daily for 28 days
Measure Participants	31	0
Geometric Mean (Full Range) [L]	1600

Adverse Events

Arm/Group Title	AZD2423 100 mg		Placebo
Arm/Group Description	Two 50 mg AZD2423 tablets, once daily for 28 days		Placebo to match AZD2423 50 mg tablets, once daily for 28 days
All Cause Mortality
	AZD2423 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD2423 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		0/32 (0%)
Cardiac disorders
Atrial Fibrillation	1/31 (3.2%)	1	0/32 (0%)	0
Atrial Flutter	1/31 (3.2%)	1	0/32 (0%)	0
Other (Not Including Serious) Adverse Events
	AZD2423 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)		2/32 (6.3%)
Gastrointestinal disorders
Dry Mouth	2/31 (6.5%)		1/32 (3.1%)
Infections and infestations
Nasopharyngitis	2/31 (6.5%)		0/32 (0%)
Nervous system disorders
Headache	2/31 (6.5%)		1/32 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.