Back to resultsAZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD)
Primary Purpose
Chronic Obstructive Pulmonary Disease, Lung Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD2423
Placebo to AZD2423
Sponsored by
About this trial
This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease focused on measuring Respiratory disease, Chronic Obstructive Pulmonary Disease
Eligibility Criteria
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.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD2423
Placebo
Arm Description
AZD2423 Oral Treatment for 28 days
Oral treatment for 28 days
Outcomes
Primary Outcome Measures
Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes
Number of all participants with clinically significant changes in laboratory variables, except monocyte, assessed at all the listed time points
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant changes in vital signs assessed at all the listed time points
Number of Participants With Clinically Significant Changes in ECG Variables
Number of participants with clinically significant changes in ECG variables assessed at all the listed time points
Number of Participants With Clinically Significant Changes in Physical Examination
Number of participants with clinically significant changes in physical examination assessed at all the listed time points
Monocytes at Baseline
Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Monocytes at End of Treatment
Monocyte count in peripheral blood at end of treatment (4 weeks)
Monocytes at Follow-up
Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)
Secondary Outcome Measures
Morning FEV1 at Baseline
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.
Morning FEV1 During Last 7 Days of Treatment
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.
Evening FEV1 at Baseline
Measurement conducted by patient in evening.
Evening FEV1 During Last 7 Days of Treatment
Measurement conducted by patient in evening.
Morning Peak Expiratory Flow (PEF) at Baseline
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.
Morning PEF During Last 7 Days of Treatment
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.
Evening PEF at Baseline
Measurement conducted by patient in evening.
Evening PEF During Last 7 Days of Treatment
Measurement conducted by patient in evening.
Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline
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.
EXACT Total Score During Last 7 Days of Treatment
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).
Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline
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.
BCSS (Evening) Total Score During Last 7 Days of Treatment
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.
Rescue Medication Use During the Last 7 Days of Treatment
Number of inhalations of short acting β2 agonist (SABA) or short acting muscarinic antagonist (SAMA) per day.
St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline
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.
SGRQ Total Score at End of Treatment
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.
CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline
Baseline = Day 1 = Visit 2
CCL2 Concentration in Plasma at End of Treatment
End of treatment = 4 weeks = Visit 6
Serum Amyloid-A (SAA) Concentration in Plasma at Baseline
Baseline = Day 1 = Visit 2
SAA Concentration in Plasma at End of Treatment
End of treatment = 4 weeks = Visit 6
Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State
PK-model: 1-compartment population model with first order absorption. AUC was estimated at steady state
Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State
PK-model: 1-compartment population model with first order absorption. Cmaxwas estimated at steady state
Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
PK-model: 1-compartment population model with first order absorption. tmax was estimated at steady state
Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
PK-model: 1-compartment population model with first order absorption. (Vss/F) was estimated at steady state
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01215279
Brief Title
AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD)
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 Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease, Lung Disease
Keywords
Respiratory disease, Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD2423
Arm Type
Experimental
Arm Description
AZD2423 Oral Treatment for 28 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral treatment for 28 days
Intervention Type
Drug
Intervention Name(s)
AZD2423
Intervention Description
100 mg oral treatment once daily for 28 days
Intervention Type
Drug
Intervention Name(s)
Placebo to AZD2423
Intervention Description
Oral treatment once daily for 28 days
Primary Outcome Measure Information:
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)
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)
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)
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)
Title
Monocytes at Baseline
Description
Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Time Frame
Day 1
Title
Monocytes at End of Treatment
Description
Monocyte count in peripheral blood at end of treatment (4 weeks)
Time Frame
week 4
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)
Secondary Outcome Measure Information:
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
Title
CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline
Description
Baseline = Day 1 = Visit 2
Time Frame
Day 1
Title
CCL2 Concentration in Plasma at End of Treatment
Description
End of treatment = 4 weeks = Visit 6
Time Frame
week 4
Title
Serum Amyloid-A (SAA) Concentration in Plasma at Baseline
Description
Baseline = Day 1 = Visit 2
Time Frame
Day 1
Title
SAA Concentration in Plasma at End of Treatment
Description
End of treatment = 4 weeks = Visit 6
Time Frame
week 4
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanna Marks-Konczalik, MD, PhD
Organizational Affiliation
AstraZeneca R&D
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Russe
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Bratislava
Country
Slovakia
Facility Name
Research Site
City
Kosice
Country
Slovakia
Facility Name
Research Site
City
Presov
Country
Slovakia
Facility Name
Research Site
City
Zilina
Country
Slovakia
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=207&filename=CSR-D3320C00002.pdf
Description
CSR-D3320C00002.pdf
Learn more about this trial
AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD)
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