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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Lung Disease
• Intervention / Treatment: Drug: AZD2423; Drug: Placebo to AZD2423

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Russe, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
• Slovakia
  • Bratislava, Slovakia
    • Research Site
  • Kosice, Slovakia
    • Research Site
  • Presov, Slovakia
    • Research Site
  • Zilina, Slovakia
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• CSR-D3320C00002.pdf

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 17, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease; Respiratory disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D3320C00002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No