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

• ClinicalTrials.gov Identifier: NCT01215279
• Recruitment Status: Completed
• First Posted: October 6, 2010
• Results First Posted: October 23, 2014
• Last Update Posted: October 23, 2014
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease; Lung Disease	Drug: AZD2423; Drug: Placebo to AZD2423	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• 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
• Study Start Date: October 2010
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes [ Time Frame: 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
2. Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: 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
3. Number of Participants With Clinically Significant Changes in ECG Variables [ Time Frame: 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
4. Number of Participants With Clinically Significant Changes in Physical Examination [ Time Frame: 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
5. Monocytes at Baseline [ Time Frame: Day 1 ]
   Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
6. Monocytes at End of Treatment [ Time Frame: week 4 ]
   Monocyte count in peripheral blood at end of treatment (4 weeks)
7. Monocytes at Follow-up [ Time Frame: week 5 (follow-up) ]
   Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)

Secondary Outcome Measures :

1. Morning FEV1 at Baseline [ Time Frame: 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.
2. Morning FEV1 During Last 7 Days of Treatment [ Time Frame: 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.
3. Evening FEV1 at Baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]
   Measurement conducted by patient in evening.
4. Evening FEV1 During Last 7 Days of Treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]
   Measurement conducted by patient in evening.
5. Morning Peak Expiratory Flow (PEF) at Baseline [ Time Frame: 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.
6. Morning PEF During Last 7 Days of Treatment [ Time Frame: 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.
7. Evening PEF at Baseline [ Time Frame: Average of 10 days of pre-treatment measurements (day -10 to -1) ]
   Measurement conducted by patient in evening.
8. Evening PEF During Last 7 Days of Treatment [ Time Frame: Average of the last 7 days of treatment (week 4) ]
   Measurement conducted by patient in evening.
9. Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline [ Time Frame: 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.
10. EXACT Total Score During Last 7 Days of Treatment [ Time Frame: 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).
11. Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline [ Time Frame: 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.
12. BCSS (Evening) Total Score During Last 7 Days of Treatment [ Time Frame: 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.
13. Rescue Medication Use During the Last 7 Days of Treatment [ Time Frame: 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.
14. St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline [ Time Frame: 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.
15. SGRQ Total Score at End of Treatment [ Time Frame: 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.
16. CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline [ Time Frame: Day 1 ]
    Baseline = Day 1 = Visit 2
17. CCL2 Concentration in Plasma at End of Treatment [ Time Frame: week 4 ]
    End of treatment = 4 weeks = Visit 6
18. Serum Amyloid-A (SAA) Concentration in Plasma at Baseline [ Time Frame: Day 1 ]
    Baseline = Day 1 = Visit 2
19. SAA Concentration in Plasma at End of Treatment [ Time Frame: week 4 ]
    End of treatment = 4 weeks = Visit 6
20. Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State [ Time Frame: 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
21. Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State [ Time Frame: 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
22. Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State [ Time Frame: 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
23. Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State [ Time Frame: 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Bulgaria

Research Site

Russe, Bulgaria

Research Site

Sofia, Bulgaria

Slovakia

Research Site

Bratislava, Slovakia

Research Site

Kosice, Slovakia

Research Site

Presov, Slovakia

Research Site

Zilina, Slovakia

Sponsors and Collaborators

AstraZeneca

Investigators

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

More Information

Additional Information:

CSR-D3320C00002.pdf 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01215279
• Other Study ID Numbers: D3320C00002
• First Posted: October 6, 2010
• Results First Posted: October 23, 2014
• Last Update Posted: October 23, 2014
• Last Verified: October 2014

Keywords provided by AstraZeneca:

Respiratory disease; Chronic Obstructive Pulmonary Disease

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases