A 4-week double-blind, placebo-controlled, randomised, parallel group phase IIa study to assess the tolerability/safety and efficacy of inhaled AZD4818 in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) - TOP

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); MedDRA version: 9.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

• Registration Number: EUCTR2007-003962-16-SE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

For inclusion in the study at Visit 1 the patients must fulfil all of the following criteria:
1. Provision of informed consent
2. Men, or women = 40 years of age. Women must be either surgically sterilised
or post-menopausal i.e. amenorrhoeic for 12 months and follicle-stimulating
hormone (FSH) plasma concentration is within the postmenopausal range as
defined by the central laboratory
3. Be able to inhale from the Turbuhaler according to given instructions
4. Body mass index between 18 and 30 kg/m2 and a minimum weight of 50 kg
5. Clinical diagnosis of COPD, with symptoms for more than 1 year
6. Current or ex-smokers with a smoking history of at least 10 pack-years (1 pack
year = 20 cigarettes smoked per day for one year)
7. FEV1 40 to 80 % of the predicted normal value (post-bronchodilator) and
post-bronchodilator FEV1/FVC < 70 %
8. Patients that can discontinue non-allowed concomitant medication.
9. A history of use of short acting ß2-agonist or anticholinergics as rescue medication
For inclusion in the study at Visit 2 the patients must fulfil all the following criterion:
1. A score = 1 on Breathlessness score on at least half of the numbers of days of
the run-in period.

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

Exclusion Criteria

Any of the following is regarded as a criterion for exclusion from the study:
1. Any clinically relevant disease or disorder (past or present), which, in the opinion
of the investigator, may either put the patient at risk because of participation in
the study, or influence the results of the study, or the patient’s ability to participate
in the study.
2. Any current respiratory tract disorder other than COPD, which is considered by
the investigator to be clinically significant or may influence the result of the study
3. A clinical suspicion of active tuberculosis (TB) defined as at least one (1) of the following:
(a) positive Mantoux-test. (>5 mm in unvaccinated individuals and >10 mm in
individuals with previous BCG-vaccination), and positive QuantiFERON®TB
Gold test (QFT), see Mori T et al 2004.
NB A QFT will only be performed after a positive Mantoux-test. If the readout of
the QFT is negative this will overrule the positive Mantoux test, hence no active
TB.
(b) suspicion of active tuberculosis on chest X-ray taken within last 6 months.
NB Abnormal chest X-ray consistent with past TB or a history of prior pulmonary,
or extrapulmonary TB, that has been adequately treated is not an exclusion criterion.
4. History of current clinically relevant arrhythmia, heart block, intraventricular
conduction delay or other clinical relevant ECG abnormalities, or unstable angina,
NYHA Class III-IV heart failure, as judged by investigator
5. Malignancy within the past 5 years
6. Disease history suggesting reduced or abnormal immune function
7. Any clinically relevant abnormal findings in physical examination, clinical
chemistry, haematology, urinalysis, vital signs or ECG at baseline, which, in
the opinion of the investigator, may put the patient at risk because of his/her
participation in the study
8. QTcF >450 ms or QT >500 ms at Visit 1
9. A history of additional risk factors for Torsade de pointes (e.g., heart failure,
hypokalemia, family history of Long QT syndrome)
10. Requirement for regular oxygen therapy
11. An exacerbation of COPD (treatment with oral or parenteral antibiotics and/or
glucocorticosteroids (GCS) and/or hospitalization related to COPD) within 30
days of Visit 1, or during the run-in period
12. Use of oral or systemic glucocorticosteroids within 30 days prior to Visit 1, or
during the run-in periodt
13. Known or suspected hypersensitivity to study therapy or excipients (e.g., benzoate,lactose) of the investigational product
14. History of or current alcohol abuse or drug abuse, as judged by the investigator
15. Participation in another study involving drug administration within 3 months
of Visit 1
16. A suspected/manifested infection according to WHO risk classification 2, 3 or 4
(See Appendix C)
17. Positive results on screening tests for hepatitis B and C
18. Known HIV infection, or patients who belong to a high risk group for HIV
19. Scheduled in-patient hospitalization during the course of the study
20. Donation of blood within 3 months or donation of plasma within 14 days prior
to Visit 1
21. Clinical judgement by the investigator that the patient should not participate in
the study
22. Previous randomization in this study
23. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the tolerability and safety of inhaled AZD4818 delivered via a dry powder inhaler, Turbuhaler®, in COPD patients by assessment of:<br>. incidence and nature of adverse events (AE)<br>. Electro Cardio Graphic (ECG) parameters, vital signs, and laboratory assessments (clinical chemistry, haematology, and urin analysis parameters).;Secondary Objective: To evaluate the effects of inhaled AZD4818 in COPD patients compared with placebo on multiple parameters.;Primary end point(s): No primary variable will be chosen. The primary objective of the study is tolerability and safety, which will be assessed by e.g. AE, ECG, vital signs, and laboratory assessments.<br>