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

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

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease, Lung Disease

Intervention / Treatment
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* Drug: AZD2423
* Drug: Placebo to AZD2423


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD2423<br>AZD2423 Oral Treatment for 28 days | Drug: AZD2423<br>* 100 mg oral treatment once daily for 28 days<br>|
| Placebo Comparator: Placebo<br>Oral treatment for 28 days | Drug: Placebo to AZD2423<br>* Oral treatment once daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | Number of participants with clinically significant changes in vital signs assessed at all the listed time points | 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 | Number of participants with clinically significant changes in ECG variables assessed at all the listed time points | 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 | Number of participants with clinically significant changes in physical examination assessed at all the listed time points | Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up) | 
| Monocytes at Baseline | Monocyte count in peripheral blood at baseline (Pre-dose, Day 1) | Day 1 | 
| Monocytes at End of Treatment | Monocyte count in peripheral blood at end of treatment (4 weeks) | week 4 | 
| Monocytes at Follow-up | Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment) | week 5 (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Average of 10 days of pre-treatment measurements (day -10 to -1) | 
| 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. | Average of the last 7 days of treatment (week 4) | 
| Evening FEV1 at Baseline | Measurement conducted by patient in evening. | Average of 10 days of pre-treatment measurements (day -10 to -1) | 
| Evening FEV1 During Last 7 Days of Treatment | Measurement conducted by patient in evening. | Average of the last 7 days of treatment (week 4) | 
| 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. | Average of 10 days of pre-treatment measurements (day -10 to -1) | 
| 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. | Average of the last 7 days of treatment (week 4) | 
| Evening PEF at Baseline | Measurement conducted by patient in evening. | Average of 10 days of pre-treatment measurements (day -10 to -1) | 
| Evening PEF During Last 7 Days of Treatment | Measurement conducted by patient in evening. | Average of the last 7 days of treatment (week 4) | 
| 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. | Average of 7 days of pre-treatment measurements (day -7 to -1) | 
| 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). | Average of the last 7 days of treatment (week 4) | 
| 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. | Average of 10 days of pre-treatment measurements (day -10 to -1) | 
| 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. | Average of the last 7 days of treatment (week 4) | 
| 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. | Average of the last 7 days of treatment (week 4) | 
| 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. | 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. | week 4 | 
| CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline | Baseline = Day 1 = Visit 2 | Day 1 | 
| CCL2 Concentration in Plasma at End of Treatment | End of treatment = 4 weeks = Visit 6 | week 4 | 
| Serum Amyloid-A (SAA) Concentration in Plasma at Baseline | Baseline = Day 1 = Visit 2 | Day 1 | 
| SAA Concentration in Plasma at End of Treatment | End of treatment = 4 weeks = Visit 6 | week 4 | 
| 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 | 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 | 
| Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State | PK-model: 1-compartment population model with first order absorption. Cmaxwas estimated at steady state | 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 | 
| 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 | 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 | 
| 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 | 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory disease, Chronic Obstructive Pulmonary Disease