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

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01215279
• Other study ID #: D3320C00002
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2010
• Last updated: October 17, 2014
• Start date: October 2010
• Est. completion date: March 2011

Study information

• Verified date: October 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug AgencyBulgaria: Ministry of HealthSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• AZD2423
100 mg oral treatment once daily for 28 days
• Placebo to AZD2423
Oral treatment once daily for 28 days

Locations

Country	Name	City	State
Bulgaria	Research Site	Russe
Bulgaria	Research Site	Sofia
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Slovakia	Research Site	Presov
Slovakia	Research Site	Zilina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Bulgaria,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)	No
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	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)	No
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	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)	No
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	Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)	No
Primary	Monocytes at Baseline	Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)	Day 1	No
Primary	Monocytes at End of Treatment	Monocyte count in peripheral blood at end of treatment (4 weeks)	week 4	No
Primary	Monocytes at Follow-up	Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)	week 5 (follow-up)	No
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.	Average of 10 days of pre-treatment measurements (day -10 to -1)	No
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.	Average of the last 7 days of treatment (week 4)	No
Secondary	Evening FEV1 at Baseline	Measurement conducted by patient in evening.	Average of 10 days of pre-treatment measurements (day -10 to -1)	No
Secondary	Evening FEV1 During Last 7 Days of Treatment	Measurement conducted by patient in evening.	Average of the last 7 days of treatment (week 4)	No
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.	Average of 10 days of pre-treatment measurements (day -10 to -1)	No
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.	Average of the last 7 days of treatment (week 4)	No
Secondary	Evening PEF at Baseline	Measurement conducted by patient in evening.	Average of 10 days of pre-treatment measurements (day -10 to -1)	No
Secondary	Evening PEF During Last 7 Days of Treatment	Measurement conducted by patient in evening.	Average of the last 7 days of treatment (week 4)	No
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.	Average of 7 days of pre-treatment measurements (day -7 to -1)	No
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).	Average of the last 7 days of treatment (week 4)	No
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.	Average of 10 days of pre-treatment measurements (day -10 to -1)	No
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.	Average of the last 7 days of treatment (week 4)	No
Secondary	Rescue Medication Use During the Last 7 Days of Treatment	Number of inhalations of short acting ß2 agonist (SABA) or short acting muscarinic antagonist (SAMA) per day.	Average of the last 7 days of treatment (week 4)	No
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.	Day 1	No
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.	week 4	No
Secondary	CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline	Baseline = Day 1 = Visit 2	Day 1	No
Secondary	CCL2 Concentration in Plasma at End of Treatment	End of treatment = 4 weeks = Visit 6	week 4	No
Secondary	Serum Amyloid-A (SAA) Concentration in Plasma at Baseline	Baseline = Day 1 = Visit 2	Day 1	No
Secondary	SAA Concentration in Plasma at End of Treatment	End of treatment = 4 weeks = Visit 6	week 4	No
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	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4	No
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	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4	No
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	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4	No
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	2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4	No

External Links

•   CSR-D3320C00002.pdf