Chronic Obstructive Pulmonary Disease, Lung Disease
Conditions
Keywords
Respiratory disease, Chronic Obstructive Pulmonary Disease
Brief summary
The purpose of the study is to investigate the tolerability and safety of AZD2423 in Patients with chronic obstructive pulmonary disease.
Interventions
DRUGAZD2423
100 mg oral treatment once daily for 28 days
DRUGPlacebo to AZD2423
Oral treatment once daily for 28 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| Monocytes at Baseline | Day 1 | Monocyte count in peripheral blood at baseline (Pre-dose, Day 1) |
| Monocytes at End of Treatment | week 4 | Monocyte count in peripheral blood at end of treatment (4 weeks) |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Evening PEF at Baseline | Average of 10 days of pre-treatment measurements (day -10 to -1) | Measurement conducted by patient in evening. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Evening PEF During Last 7 Days of Treatment | Average of the last 7 days of treatment (week 4) | Measurement conducted by patient in evening. |
| CCL2 Concentration in Plasma at End of Treatment | week 4 | End of treatment = 4 weeks = Visit 6 |
| Serum Amyloid-A (SAA) Concentration in Plasma at Baseline | Day 1 | Baseline = Day 1 = Visit 2 |
| SAA Concentration in Plasma at End of Treatment | week 4 | 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 | 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 |
| 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 |
| 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 |
| 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 |
| CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline | Day 1 | Baseline = Day 1 = Visit 2 |
| 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. |
| 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. |
| Evening FEV1 at Baseline | Average of 10 days of pre-treatment measurements (day -10 to -1) | Measurement conducted by patient in evening. |
| Evening FEV1 During Last 7 Days of Treatment | Average of the last 7 days of treatment (week 4) | Measurement conducted by patient in evening. |
| 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. |
| 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. |
Countries
Bulgaria, Slovakia
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.
Participants by arm
| Arm | Count |
|---|---|
| AZD2423 100 mg Two 50 mg AZD2423 tablets, once daily for 28 days | 31 |
| Placebo Placebo to match AZD2423 50 mg tablets, once daily for 28 days | 32 |
| Total | 63 |
Baseline characteristics
| Characteristic | AZD2423 100 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.5 Years STANDARD_DEVIATION 7.8 | 60.6 Years STANDARD_DEVIATION 7.2 | 61.6 Years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 24 Participants | 23 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 31 | 2 / 32 |
| serious Total, serious adverse events | 2 / 31 | 0 / 32 |
Outcome results
Primary
Monocytes at Baseline
Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Monocytes at Baseline | 0.47 10^9/L | Standard Deviation 0.136 |
| Placebo | Monocytes at Baseline | 0.43 10^9/L | Standard Deviation 0.143 |
Primary
Monocytes at End of Treatment
Monocyte count in peripheral blood at end of treatment (4 weeks)
Time frame: week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Monocytes at End of Treatment | 0.43 10^9/L | Standard Deviation 0.165 |
| Placebo | Monocytes at End of Treatment | 0.55 10^9/L | Standard Deviation 0.178 |
Primary
Monocytes at Follow-up
Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)
Time frame: week 5 (follow-up)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Monocytes at Follow-up | 0.50 10^9/L | Standard Deviation 0.175 |
| Placebo | Monocytes at Follow-up | 0.52 10^9/L | Standard Deviation 0.196 |
Primary
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
Time frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 100 mg | Number of Participants With Clinically Significant Changes in ECG Variables | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in ECG Variables | 0 Participants |
Primary
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
Time frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 100 mg | Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes | 0 Participants |
Primary
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
Time frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 100 mg | Number of Participants With Clinically Significant Changes in Physical Examination | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Physical Examination | 0 Participants |
Primary
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
Time frame: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 100 mg | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
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
Time frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State | 1600 L |
Secondary
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
Time frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State | 2780 nmol*h/L |
Secondary
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.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | BCSS (Evening) Total Score During Last 7 Days of Treatment | 5.1 Units on scale, 0-12 | Standard Deviation 1.68 |
| Placebo | BCSS (Evening) Total Score During Last 7 Days of Treatment | 5.1 Units on scale, 0-12 | Standard Deviation 2.25 |
Secondary
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.
Time frame: Average of 10 days of pre-treatment measurements (day -10 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline | 5.2 Units on scale, 0-12 | Standard Deviation 1.4 |
| Placebo | Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline | 5.3 Units on scale, 0-12 | Standard Deviation 1.82 |
Secondary
CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline
Baseline = Day 1 = Visit 2
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline | 294 pg/mL |
| Placebo | CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline | 279 pg/mL |
Secondary
CCL2 Concentration in Plasma at End of Treatment
End of treatment = 4 weeks = Visit 6
Time frame: week 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | CCL2 Concentration in Plasma at End of Treatment | 1286 pg/mL |
| Placebo | CCL2 Concentration in Plasma at End of Treatment | 272 pg/mL |
Secondary
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 frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State | 198 nmol/L |
Secondary
Evening FEV1 at Baseline
Measurement conducted by patient in evening.
Time frame: Average of 10 days of pre-treatment measurements (day -10 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Evening FEV1 at Baseline | 1.3 L | Standard Deviation 0.43 |
| Placebo | Evening FEV1 at Baseline | 1.4 L | Standard Deviation 0.44 |
Secondary
Evening FEV1 During Last 7 Days of Treatment
Measurement conducted by patient in evening.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Evening FEV1 During Last 7 Days of Treatment | 1.2 L | Standard Deviation 0.37 |
| Placebo | Evening FEV1 During Last 7 Days of Treatment | 1.4 L | Standard Deviation 0.51 |
Secondary
Evening PEF at Baseline
Measurement conducted by patient in evening.
Time frame: Average of 10 days of pre-treatment measurements (day -10 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Evening PEF at Baseline | 192.3 L/minute | Standard Deviation 74.27 |
| Placebo | Evening PEF at Baseline | 196.2 L/minute | Standard Deviation 79.92 |
Secondary
Evening PEF During Last 7 Days of Treatment
Measurement conducted by patient in evening.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Evening PEF During Last 7 Days of Treatment | 191.9 L/minute | Standard Deviation 82.17 |
| Placebo | Evening PEF During Last 7 Days of Treatment | 204.7 L/minute | Standard Deviation 87.98 |
Secondary
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.
Time frame: Average of 7 days of pre-treatment measurements (day -7 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline | 44.4 Units on scale, 0-100 | Standard Deviation 6.99 |
| Placebo | Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline | 45.7 Units on scale, 0-100 | Standard Deviation 8.49 |
Secondary
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).
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | EXACT Total Score During Last 7 Days of Treatment | 43.8 Units on scale, 0-100 | Standard Deviation 7.78 |
| Placebo | EXACT Total Score During Last 7 Days of Treatment | 44.6 Units on scale, 0-100 | Standard Deviation 9.84 |
Secondary
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.
Time frame: Average of 10 days of pre-treatment measurements (day -10 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Morning FEV1 at Baseline | 1.3 L | Standard Deviation 0.41 |
| Placebo | Morning FEV1 at Baseline | 1.3 L | Standard Deviation 0.44 |
Secondary
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.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Morning FEV1 During Last 7 Days of Treatment | 1.3 L | Standard Deviation 0.4 |
| Placebo | Morning FEV1 During Last 7 Days of Treatment | 1.4 L | Standard Deviation 0.52 |
Secondary
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.
Time frame: Average of 10 days of pre-treatment measurements (day -10 to -1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Morning Peak Expiratory Flow (PEF) at Baseline | 190.5 L/minute | Standard Deviation 74.73 |
| Placebo | Morning Peak Expiratory Flow (PEF) at Baseline | 185.5 L/minute | Standard Deviation 74.21 |
Secondary
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.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Morning PEF During Last 7 Days of Treatment | 190.2 L/minute | Standard Deviation 77.24 |
| Placebo | Morning PEF During Last 7 Days of Treatment | 196.4 L/minute | Standard Deviation 83.81 |
Secondary
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.
Time frame: Average of the last 7 days of treatment (week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | Rescue Medication Use During the Last 7 Days of Treatment | 4.0 Inhalations | Full Range 1 |
| Placebo | Rescue Medication Use During the Last 7 Days of Treatment | 3.5 Inhalations | Full Range 1 |
Secondary
SAA Concentration in Plasma at End of Treatment
End of treatment = 4 weeks = Visit 6
Time frame: week 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | SAA Concentration in Plasma at End of Treatment | 6325 ng/mL |
| Placebo | SAA Concentration in Plasma at End of Treatment | 4032 ng/mL |
Secondary
Serum Amyloid-A (SAA) Concentration in Plasma at Baseline
Baseline = Day 1 = Visit 2
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2423 100 mg | Serum Amyloid-A (SAA) Concentration in Plasma at Baseline | 5175 ng/mL |
| Placebo | Serum Amyloid-A (SAA) Concentration in Plasma at Baseline | 4044 ng/mL |
Secondary
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.
Time frame: week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | SGRQ Total Score at End of Treatment | 52.0 Percent of maximum possible score | Standard Deviation 14.38 |
| Placebo | SGRQ Total Score at End of Treatment | 52.9 Percent of maximum possible score | Standard Deviation 18.04 |
Secondary
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.
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 100 mg | St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline | 55.9 Percent of maximum possible score | Standard Deviation 14.96 |
| Placebo | St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline | 57.0 Percent of maximum possible score | Standard Deviation 19.27 |
Secondary
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
Time frame: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD2423 100 mg | Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State | 1.01 Hours |