A 12-week, Phase-II, Double-Blind, Placebo-Controlled, Randomised,Parallel-Group, Multi-Centre Study to Assess the Effect of 60 mg AZD9668Administered Orally Twice Daily on Structural Changes in the Airwaysby Multi-Slice Computed Tomography (MSCT) in Patients with ChronicObstructive Pulmonary Disease (COPD)
- Conditions
- MedDRA version: 12.0Level: LLTClassification code 10010952Term: COPDChronic Obstructive Pulmonary Disease (COPD)
- Registration Number
- EUCTR2009-014594-40-DK
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
1. Provision of informed consent prior to any study specific procedures at Visit 1a.
2. Male or female aged 50-80 years inclusive at Visit 1b.
Female patients may be of non-childbearing potential (i.e. post menopausal or
surgically sterile) or of child bearing potential:
- Women will be considered post menopausal if they are
i) over 50 years old and have been amenorrheic for 12 months or more
following cessation of all exogenous hormonal treatments or
ii) over 57 years old
- Surgically sterile is defined as having undergone hysterectomy and/or bilateral
oophrectomy and/or bilateral salpingectomy; tubal ligation on its own is not
adequate
- Women will be considered of child bearing potential if they are between
menarche and menopause, and have not been permanently or surgically
sterilised. Women of child bearing potential must have a pregnancy test at
visit 1b and at visit 2 prior to randomisation, and at the follow up visit, and
must be using suitable methods of birth control. Further details of methods of
birth control that are considered suitable for use are given in Section 5.1. in the protocol.
3. Documented clinical diagnosis of COPD, according to GOLD guidelines
(GOLD 2008) with symptoms for =1 year before Visit 1b.
4. Ex-smokers for at least 12 months prior to Visit 1b.
5. A smoking history of at least 10 pack years (1 pack year = tobacco consumption
corresponding to 20 cigarettes smoked per day for 1 year).
6. FEV1 40-70% (inclusive) of the predicted normal value (post-bronchodilator) at
Visit 1b.
7. FEV1/FVC <70% (post-bronchodilator) at Visit 1b.
8. Able to use the handheld electronic devices (assessed at Visit 1a).
For randomisation into the study at Visit 2 the patients must also fulfil the following criteria:
1. MSCT performed during the last 2 to 7 days before randomisation with acceptable
quality and the whole lung is visible on the images, as judged by the radiologist
visual read.
2. No clinically relevant abnormal findings in baseline CT besides CT changes
related to COPD, (e.g. congestive heart failure, lung cancer, tuberculosis, lung
fibrosis, sarcoidosis, cystic fibrosis) which in the opinion of the Investigator, may
put the patient at risk because of his/her participation in the study, or may influence
the results of the study, or the patient’s ability to participate in the study.
3. Complete morning recordings of daily FEV1 data at least 10 days out of the last
14 days before Visit 2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Any clinically relevant disease or disorder (e.g. infectious/viral disease (including
hepatitis B or C) cardiovascular, pulmonary other than COPD, gastrointestinal,
liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant,
psychiatric, major physical impairment), past or present, which in the opinion
of the Investigator, may either put the patient at risk because of participation in
the study, or may influence the results of the study, or the patient’s ability to
participate in the study.
2. Significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart
failure, uncontrolled hypertension, or any other relevant cardiovascular disorder
as judged by the Investigator.
3. Current diagnosis of asthma according to GINA guidelines (GINA 2008).
4. Malignancy or neoplastic disease within the past 5 years other than treated
basal/squamous cell skin carcinoma or treated cervical cancer in situ.
5. Patients who require long term oxygen therapy (LTOT).
6. Worsening of COPD within 4 weeks prior to Visit 1b and during the run-in period
(defined as an increase in respiratory symptoms requiring hospitalisation and/or a
course of oral glucocorticosteroids and/or increased usage/dose of inhaled steroids
and/or antibiotic treatment).
7. Acute infections requiring treatment in the 4 weeks prior to Visit 1b and during
the run-in period.
8. Any clinically relevant abnormal findings in physical examination, vital signs,
haematology, clinical chemistry, or urinalysis at Visit 1b, which in the opinion
of the Investigator, may put the patient at risk because of his/her participation
in the study, or may influence the results of the study, or the patient’s ability to
participate in the study.
9. A QTcB interval of >450 msec for males and >470 msec for females at Visit 1b.
10. Any ECG abnormality (including arrhythmia), which in the opinion of the
investigator may put the patient at risk or interfere with study assessments at
Visit 1b.
11. A past history of or current clinical or laboratory evidence of renal failure,
or an estimated creatinine clearance of <50 mL/min (as calculated by the
Cockcroft-Gault formula) at Visit 1b.
12. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level
=1.5 x upper limit of normal (ULN) at Visit 1b.
13. Pregnancy, breast-feeding or planned pregnancy during the study.
14. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
15. Previous randomisation to treatment in the present study.
16. Previous participation in a study with AZD9668.
17. Participation (defined as administration of at least 1 dose of investigational
product) in another clinical study, the last follow-up visit of which is within 12
weeks of Visit 1b in this study.
18. Excessive alcohol consumption or known drug abuse, as judged by the investigator.
19. Scheduled in patient surgery or hospitalisation during the course of the study.
20. Patients scheduled for an intensive COPD rehabilitation programme. (Patients
who are in the maintenance phase of a rehabilitation programme are eligible to
take part.)
21. Known or suspected hypersensitivity to the investigational product or excipients
or additional non-investigational study drugs provided for the study (tiotropium
and reliever medication).
22. Patients with conditions that may worsen if treated with tiotropium, according to
the prescribing information for tiotropium
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate structural changes effected by AZD9668 in the airways of adults with Chronic Obstructive Pulmonary Disease (COPD) by Multi-Slice Computed Tomography (MSCT).;Secondary Objective: The secondary objectives of the study are:<br><br>To relate structural changes in the airways to pulmonary function variables and<br>symptoms of COPD.<br><br>To evaluate safety of AZD9668 in COPD patients;Primary end point(s): AWT-Pi10 (airway wall thickness of a theoretical airway with an internal perimeter<br>of 10 mm)
- Secondary Outcome Measures
Name Time Method