E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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).
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of database lock, which is the timepoint after which no patient will be exposed to study-related activities. This has been selected as the definition of the end of the study to ensure consistency with trials conducted outside the European Union. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |