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

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-004110-32-GB
• Date of registration: 22/09/2005
• Prospective Registration: Yes
• 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
• 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
• Date of first enrolment: 01/12/2005
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): 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 (documented in patient notes) for more than 2 years
5. Patients must not be at risk of active tuberculosis including disease reactivation as indicated by a negative result in all 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)
(iii) Positive T SPOT™ -TB (Elispot) test
(iv) Chest x-ray (taken within the previous 2 years) suggesting healed or active TB
6. Current or ex-smokers with a smoking history of at least 10 years
7. FEV1 of 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%
When the patient returns to clinic for Visit 2, the following criteria should be fulfilled before they are considered eligible for randomisation.
8. Sputum producers with a history of chronic expectoration on most days of most weeks of the year (sputum colour, as recorded by the study site staff at Visit 2, of grade =3 (Bronkotest© diary card)
9. Patients must have a daily score for amount of sputum produced (from Bronkotest© diary card) of =2, for any 7 consecutive days during the baseline period (from Visit 1)
10. Patients must not have experienced exacerbation of their COPD since Visit 1
11. 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
12. Patients must not have taken any disallowed medications during the baseline period (since signing consent)
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:
1. Pregnant or lactating females
2. A history of asthma or seasonal allergic rhinitis with disease onset before 40 years of age
3. Concomitant diagnosis of clinical bronchiectasis, sarcoidosis or pulmonary disease other than COPD
4. Requirements for regular oxygen therapy
5. 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
6. Known HIV infection or positive tests for Hepatitis B or C
7. 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
8. Use of antibiotics within 4 weeks of Visit 1
9. Receipt of live, or live attenuated, vaccines within 4 weeks of Visit 1
10. 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)
11. Chronic liver or renal disease
12. 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
13. 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
14. 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)
15. Abnormal ECG for this patient population, as judged by the investigator including a QTc >450 ms
16. History of retinopathy
17. A history of hypersensitivity or intolerance to any ingredient in the investigational product
18. Use of disallowed medications (See Section 3.7.1 for detailed list)
19. Scheduled in-patient surgery or hospitalisation during the course of the study
20. History of or current drug abuseas judged by the investigator
21. Participation in another clinical study involving an investigational product within 90 days of Visit 1
22. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
23. Previous enrolment or randomisation to treatment in the present study



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
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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).

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): The primary variables are exercise tolerance compared to baseline as captured by the 6MWT, symptoms compared to baseline (captured on Bronkotest diary card, Baseline Dyspnoea Index (BDI)/Transition Dyspnoea Index (TDI)), lung function change from baseline, inflammatory markers in blood and sputum and quality of life compared to baseline, as captured by SGRQ.

Secondary ID(s)

D1521C00002

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 14/07/2016
• Date Completed: 29/09/2006
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-004110-32/results