E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a Phase IIIB study to be performed in adult and adolescent asthmatic patients. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10003553 |
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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 of this study is to compare the efficacy of two inhalations of Symbicort Turbuhaler 160/4.5 µg/inhalation twice daily plus Symbicort Turbuhaler 160/4.5 µg/inhalation as-needed, with one inhalation of Seretide Diskus 50/500 µg/inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as-needed in patients with persistent asthma by evaluation of time to first severe asthma exacerbation as the primary outcome variable. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to investigate safety by assessing the nature, incidence, and severity of adverse events within the treatment groups. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
For inclusion in the study run-in period, patients must fulfill all of the following criteria at Visit 1: 1. Provision of informed consent. The signed and dated informed consent must have been obtained before conducting any study-related procedures, including withdrawal of concomitant medication (consent can be obtained at an information visit or at Visit 1). For patients under-age, signed informed consent from both the patient and the patient’s parent/legal guardian is required. 2. Outpatients of either sex, ≥12 years of age. 3. Minimum of 6 months’ documented history of asthma according to the American Thoracic Society definition (ATS 1987). 4. Pre-bronchodilatory FEV1 ≥50% of predicted normal values. 5. Reversible airway obstruction (according to reversibility test performed at Visit 1), defined as an increase in FEV1 ≥12% relative to baseline (for all patients) and for patients ≥18 years ≥200 mL after inhalation of in total 1 mg Bricanyl Turbuhaler. 6. Prescribed daily use of inhaled GCS for ≥3 months prior to Visit 1. 7. During the last 30 days prior to Visit 1, the daily prescribed dose of inhaled GCS should have been constant and between: - 400-1000 µg metered dose, or the corresponding delivered dose, in combination with LABA - 800-1600 µg metered dose, or the corresponding delivered dose, if used without LABA. 8. A history of at least one clinically important asthma exacerbation, as judged by the investigator, between ≥1 but ≤12 months prior to Visit 1.
To be randomised to the treatment period, the following criteria must be fulfilled at Visit 2: 9. Use of as-needed medication on at least 5 of the last 7 days of the run-in period. 10. The patient must not have taken more than 8 inhalations of as-needed medication on any day during the run-in period. 11. The patient must not have had a clinically important asthma exacerbation, as judged by the investigator, during the run-in period. 12. Ability to fill in the diary correctly, and to use peak flow meter, Turbuhaler and Diskus inhalers correctly. 13. The patient must still be eligible for the study in accordance with the exclusion criteria.
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E.4 | Principal exclusion criteria |
1. Known or suspected hypersensitivity to active substance or lactose monohydrate. 2. Respiratory infection affecting the asthma, as judged by the investigator, within 30 days prior to Visit 1. 3. Intake of oral, rectal, or parenteral GCS within 30 days prior to Visit 1. 4. Use of any β-blocking agent, including eye-drops. 5. A history of smoking ≥10 pack-years (one pack-year = one pack (20 cigarettes) per day for one year or equivalent). 6. Pregnancy, breast-feeding, or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator. 7. Any significant disease or disorder (eg, cardiovascular, pulmonary other than asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, either put the patient at risk because of participating in the study or may influence the results of the study, or the patient’s ability to participate in the study. 8. Any non-asthma-related clinically significant abnormal finding in physical examination or vital signs at Visit 1, as judged by the investigator. 9. Suspected poor capability, as judged by the investigator, to follow instructions of the study, eg, because of a history of alcohol or drug abuse. 10. Planned in-patient hospitalisation during the course of the study. 11. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational study site). 12. Previous allocation of randomisation code in the study. 13. Participation in a clinical study during the course of this study or within 30 days prior to Visit 1. 14. Inability to tolerate withdrawal of asthma therapy as required for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is time to first severe asthma exacerbation.
A severe asthma exacerbation is defined as deterioration in asthma leading to at least one of the following: - hospitalisation/emergency room (or equivalent) treatment due asthma - oral GCS treatment due to asthma for at least 3 days.
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | No |
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 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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |