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

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease
Lung Disease

Interventions: Drug: AZD2423
Drug: Placebo to AZD2423

Registration Number: NCT01215279

Lead Sponsor: AstraZeneca

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZD2423	AZD2423	AZD2423 Oral Treatment for 28 days
Placebo	Placebo to AZD2423	Oral treatment for 28 days

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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.
Evening PEF at Baseline	Average of 10 days of pre-treatment measurements (day -10 to -1)	Measurement conducted by patient in evening.
Evening PEF During Last 7 Days of Treatment	Average of the last 7 days of treatment (week 4)	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.
CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline	Day 1	Baseline = Day 1 = Visit 2
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.
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