A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase II Study to Assess The Efficacy of AZD9056 (single oral 400 mg dose) when Administered for 4 Weeks in Patients with Moderate to Severe COPD - PACE

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-004110-32-DE
• Date of registration: 06/03/2006
• Prospective Registration: No
• Primary sponsor: AstraZeneca AB
• Public title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase II Study to Assess The Efficacy of AZD9056 (single oral 400 mg dose) when Administered for 4 Weeks in Patients with Moderate to Severe COPD - PACE
• Scientific title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase II Study to Assess The Efficacy of AZD9056 (single oral 400 mg dose) when Administered for 4 Weeks in Patients with Moderate to Severe COPD - PACE
• Date of first enrolment: 03/03/2006
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004110-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Hungary, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of signed and dated informed consent (prior to any study-related
procedures or restrictions)
2. Male or female aged between 40 to 80 years
3. Females must be using 2 forms of contraception (eg, oral contraception and barrier
method) for the duration of the study, unless they are surgically sterile or
post-menopausal
4. Clinical diagnosis of COPD
5. Sputum producers with a history of chronic expectoration on most days of most
weeks of the year. Patients must produce at least 3 g of sputum during the morning
of Visit 1. (If this criterion is not fulfilled and it is felt that the weight does not
represent the normal sputum production for a particular patient, Visit 1 may be
deferred once only to allow the sputum assessment to be repeated.)
If the patient has fulfilled criteria 1-5, the following criteria should be assessed:
6. Patients must not be at risk of active tuberculosis including disease reactivation as
indicated by any of the following:
(i) Past medical history of TB or current symptoms suggestive of active TB
(ii) A positive tuberculin (Mantoux) test in response to intradermally dosed
tuberculin (either PPD RT23 SSI, 2 Tuberculin units/0.1 mL, solution for
injection (SSI, Copenhagen Denmark) or an equivalent local tuberculin
preparation). The following limits apply when using SSI tuberculin: 05 mm
= negative, =6 mm = positive for non-BCG immunised patients, =15 mm =
positive for BCG immunised patients.
(iii) Positive T SPOT ™ -TB (Elispot) test
(iv) Chest x-ray (taken within the previous 2 years) suggesting healed or active
TB
7. Current or ex-smokers with a smoking history of at least 10 pack years
8. FEV1 of >0.7 L and 30-60% of the predicted normal value (pre-bronchodilator),
according to the European Community for Coal and Steel, and a FEV1/FVC ratio of
<70%. (If the patient has taken specific bronchodilators prior to the test within the
washout periods, this may be deferred but must be
completed prior to Visit 2.)
When the patient returns to clinic for Visit 2, the following criteria should be fulfilled before
they are considered eligible for randomisation.
9. Sputum colour, as recorded by the study site staff at Visit 2 (all patients) and
additionally Visit 1.2 for the sputum inflammatory marker sub-group, of grade =3
(Bronkotest © diary card) and sputum weight in all instances should be =3 g.
10. Patients must have a daily score for amount of sputum produced (from Bronkotest ©
diary card) of =1, for at least 7 consecutive days during the baseline period (from
Visit 1)
11. Patients must not have experienced exacerbation of their COPD since Visit 1
12. During the baseline period, patients must have been able to show that they have
completed the diary card satisfactorily and that they are willing and able to
complete all remaining study procedures
13. Patients must not have taken any disallowed medications during the baseline 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. Pregnant or lactating females
2. A history of asthma
3. A history of seasonal allergic rhinitis with disease onset before 40 years of age
4. Concomitant diagnosis of clinical bronchiectasis, sarcoidosis or pulmonary disease
other than COPD
5. Requirements for regular oxygen therapy
6. Any other clinically significant disease or disorder (including insulin-dependent
diabetes and active peptic ulceration) which, in the opinion of the investigator, may
either put the subject at risk because of participation in the study, or may influence
the results of the study, or the subject’s ability to participate in the study
7. Known HIV infection or patients who belong to a high risk group for HIV or
positive tests for Hepatitis B or C
8. An exacerbation of COPD (defined as, an increase in respiratory symptoms
requiring hospitalisation and/or a course of oral glucocorticosteroids and/or
antibiotics (either prescribed or self-administered) within 8 weeks of Visit 1
9. Use of antibiotics within 4 weeks of Visit 1 for a reason other than COPD
10. Receipt of live, or live attenuated, vaccines within 4 weeks of Visit 1
11. History of malignancy and neoplastic disease (however, patients who have been
successfully treated for basal or squamous cell carcinoma of the skin more than
5 years ago, may be included)
12. Chronic liver or renal disease
13. Liver function tests (Aspartate aminotransferase (AST), Alanine aminotransferase
(ALT) or bilirubin) above the upper limit of normal (ULN) of central laboratory
reference range at Visit 1
14. Any clinically significant deviations (as judged by the investigator) from the central
laboratory reference ranges for other clinical chemistry, or haematology parameters
at Visit 1
15. History of excessive alcohol consumption or current consumption of more than
28 units per week (male) or 21 units per week (female). (One unit of alcohol is
equivalent to half a pint of ordinary strength beer, lager, or cider; a quarter of a pint
of strong beer or lager; one small glass of wine; one single measure of spirits). This
will be judged by the Investigator
16. Abnormal ECG for this patient population, as judged by the investigator including a
QTc >450 ms
17. History of retinopathy
18. A history of hypersensitivity or intolerance to any ingredient in the investigational
product
19. Use of disallowed medications (See Section 3.7.1 for detailed list)
20. Scheduled in-patient surgery or hospitalisation during the course of the study
21. History of or current drug abuse, as judged by the investigator
22. Participation in another clinical study involving an investigational product within
90 days of Visit 1
23. Involvement in the planning and conduct of the study (applies to both AstraZeneca
staff or staff at the study site)
24. Previous enrolment or randomisation to treatment in the present study
25. History of recurrent or chronic infection (eg, sinusitis, UTI, genital herpes) or
patients with chronic eczema (ie, increased carriage of S. aureus).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease

Intervention(s)

Product Name: AZD9056
Product Code: AZD9056
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the study is to determine the efficacy of AZD9056 (single oral
400 mg dose) in moderate to severe COPD patients, during a 4-week treatment period.

Primary end point(s): •6MWT change from baseline (Visit 2) to Visit 4
•TDI at Visit 4
•PEF, symptom scores and sputum scores (including amount and colour) as recorded
on the Bronkotest © diary card change from the mean of the baseline period to the
mean of the last 7 days. Sputum weight and colour as recorded at Visit 4 (change
from baseline Visit 2).
•Lung function responses (SVC, FEV1, FVC and IC) change from baseline (Visit 2)
to Visit 4
Inflammatory markers in sputum (including Neutrophil counts) The change from
the mean of the duplicate samples at baseline to the mean of the duplicate samples
taken at the end of the treatment period (see pharmacodynamic section below for
details)
•Inflammatory markers in blood change from baseline to Visit 4 (see
pharmacodynamic section below for details)
•SGRQ change from baseline (Visit 2) to Visit 4.

Secondary Objective: 1. To determine the safety and tolerability (recording of AEs, safety laboratory data and ECGs) of AZD9056 in COPD patients
2. To determine the PK of AZD9056 in patients with moderate to severe COPD by measurement of pre-dose (trough) and post-dose plasma concentrations and estimation of clearance (CL/F) and volume of distribution (Vss/F).

Secondary ID(s)

D1521C00002

2005-004110-32-GB