E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Chronic Obstructive Pulmonary Disease (COPD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
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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 is to evaluate early morning efficacy of Symbicort Turbuhaler 320/9 µg one inhalation twice daily compared to Seretide Diskus 50/500 µg one inhalation twice daily in patients with severe COPD over one week treatment.
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate safety by assessing the nature and incidence of adverse events (AEs). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study patients must fulfil all of the following criteria: 1. Provision of informed consent prior to conducting any study-related procedures. 2. Outpatient, female or male aged ≥40 years. 3. A clinical diagnosis of COPD with symptoms for more than 2 years, prior to visit 2. 4. A current or previous smoker with a smoking history ≥10 pack years (1 pack year = 20 cigarettes smoked per day for one year). 5. FEV1 ≤50% of predicted normal value, pre-bronchodilator. 6. FEV1/VC <70%, pre-bronchodilator. 7. Previous use of a short-acting inhaled bronchodilator (β2-agonist or anticholinergics) as reliever medication. 8. A history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1 to 12 months prior to visit 2. 9. Able to read and write and use the electronic devices (eDiary and ePEF).
To be randomised the patient must fulfil the following criteria at Visit 3:
10. Total morning symptoms score of at least 2 (GCSQ score) on 5 out of the last 7 days of the run-in period, excluding day of visit 3. 11. Complete morning records of PEF data on at least 5 out of the last 7 days of the run-in period, excluding day of visit 3.
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E.4 | Principal exclusion criteria |
Any of the following is regarded as a criterion for exclusion from the study:
1. A history of asthma. 2. A history of seasonal allergic rhinitis before 40 years of age. 3. Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the investigator, or any other relevant cardiovascular disorder, as judged by the investigator. 4. Any current respiratory tract disorder other than COPD, which is considered by the investigator to be clinically significant. 5. Any significant disease or disorder 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 patients ability to participate in the study. 6. Patients taking oral or ophthalmic non-cardioselective β-blocking agents. 7. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator. 8. Regular oxygen therapy. 9. Known or suspected hypersensitivity to study therapy or excipients of the investigational products. 10. Scheduled in-patient hospitalization during the course of the study. 11. Patients who have participated in a clinical study evaluating an investigational drug in the last 4 weeks (3 months in the UK) prior to visit 2, or who have been previously allocated a randomisation code in this study. 12. Patients with a history of chronic alcohol or drug abuse or any condition associated with poor compliance. 13. Patient participating in or scheduled for an intensive COPD rehabilitation programme during the course of the study. 14. Any clinically relevant abnormal findings in clinical, physical examination, and vital signs at Visit 2, which in the opinion of the investigator(s) may put the patient at risk because of his/her participation in the study (to be checked before allocation of randomisation code at Visit 3). 15. Exacerbation of COPD during run-in or within 4 weeks prior to visit 2 (from end of exacerbation), requiring hospitalisation, a course of oral and/or increased doses of inhaled steroids and/or antibiotics. 16. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 17. Use of oral/parenteral glucocorticosteroids within 4 weeks prior to Visit 2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be Peak Expiratory Flow (PEF) 5 minutes after morning dose. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Reported Outcome (Health related Quality of Life) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double dummy technique for blinding |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 | No |
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 date of database lock, which is the time point after which no patient will be exposed to study related activities. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |