| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| 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 |
| To demonstrate that Symbicort Turbuhaler 160/4.5 µg ‘as needed’ is non-inferior to Pulmicort Turbuhaler 200 µg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’ |
|
| E.2.2 | Secondary objectives of the trial |
To estimate the difference in efficacy between Symbicort Turbuhaler 160/4.5 μg ‘as needed’ and Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’
To compare the safety of Symbicort Turbuhaler 160/4.5 μg ‘as needed’ with that of Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’ |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient’s parent/legal guardian is required
2. Outpatients of either gender aged ≥12 years at Visit 1
3. Diagnosis of asthma according to GINA criteria with a documented history of at least 6 months prior to Visit 1
4. Patients who are in need of GINA step 2 treatment:
- uncontrolled on an inhaled short acting bronchodilator(s) "as needed" (short acting beta2 agonist and/or short acting anticholinergic agent) as judged by the investigator for the last 30 days before Visit 2, or
- controlled on mono-maintenance therapy with low stable dose ICS (≤ 400 μg budesonide per day or corresponding dose of other ICS) (see Appendix E for conversion) or LTRA in addition to "as needed" use of inhaled short-acting bronchodilator (short acting beta2 agonist and/or short acting anticholinergic agent) as judged by the investigator for the last 30 days prior to Visit 2
5. Based on lung function tests (see Section 5.1.2) at Visit 2, patients pre-treated with
- a SABA only should have pre-bronchodilator FEV1 ≥ 60 % of predicted normal (PN) and post- bronchodilator FEV1 ≥ 80 % of PN according to the European Respiratory Society (ERS) guidelines (Quanjer at al 2012)
- low dose ICS or LTRA medication should have pre-bronchodilator FEV1 ≥80 % PN according to the ERS guidelines
6. Reversible airway obstruction according to a reversibility test (see Section 5.1.2.2) performed at Visit 2 defined as an increase in FEV1 ≥12% and ≥200 ml relative to baseline, after inhalation of 1 mg Bricanyl Turbuhaler. The test can be repeated at Visit 3 in case the patients fail at Visit 2. If patients fail at both occasions, they can still be included if they have a documented historical reversibility test within the last 12 months prior to Visit 3, with an increase in FEV1 ≥12% and ≥200 ml relative to baseline after administration of a rapid acting β2-agonist.
For randomisation at Visit 3, patients should fulfil the following criteria:
7. Use of Bricanyl Turbuhaler ‘as needed’ due to asthma symptoms on at least 3 separate days during the last week of the run-in period
8. Ability to use Turbuhaler correctly.
|
|
| E.4 | Principal exclusion criteria |
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2. Previous randomisation in the present study or in the study D589SC00001 (SYGMA 1)
3. Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug during the last 30 days prior to Visit 1
4. Participation in another clinical trial with any marketed or investigational biologic drug within 4 months or 5 half-lives whichever is longer, prior to Visit 1
5. Any asthma worsening requiring change in asthma treatment other than SABA within 30 days prior to Visit 1
6. Use of oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1
7. Use of any β-blocking agent including eye-drops
8. Known or suspected hypersensitivity to study drugs or excipient
9. Smoker (current or previous) with a smoking history of ≥ 10 pack years
10. Medical history of life-threatening asthma including intubation and intensive care unit admission
11. Any significant disease or disorder (e.g., cardiovascular, pulmonary other than asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) 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 patient’s ability to participate in the study
12. Any clinically relevant abnormal findings in physical examination and/or vital signs at Visit 2, which, in the opinion of the investigator, may put the patient at risk if participating in the study
13. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator
14. Planned hospitalisation during the study
15. Suspected poor capability, as judged by the investigator, of following instructions of the study
For randomisation at Visit 3, patients should not fulfil any of the following criteria:
16. Use of ≥ 6 Bricanyl Turbuhaler ‘as needed’ inhalations per day, for a certain number of days depending on the actual length of run-in: for ≥ 2 days out of 14 days; for ≥ 3 days out of 15-21 days; for ≥ 4 days out of 22 or more days of run-in
17. Any asthma worsening requiring change in treatment other than SABA from Visit 1 until randomisation.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Annual severe asthma exacerbation rate |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Time to first severe asthma exacerbation
•Average change from baseline in pre-dose FEV1
•Time to study specific asthma related discontinuation
•Average change from baseline in ‘as needed’ use
•Change from baseline in percent of ‘as needed’ free days
•Percentage of controller use days
•Average change from baseline in Asthma Control Questionnaire (5-item version) - ACQ-5 score
•Average change from baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) score
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 52 weeks
Time to first severe asthma exacerbation
Time to study specific asthma related discontinuation
Average change from baseline in ‘as needed’ use
Change from baseline in percent of ‘as needed’ free days
Percentage of controller use days
Study weeks 0,17,34,52
Average change from baseline in pre-dose FEV1
Average change from baseline in Asthma Control Questionnaire (5-item version) - ACQ-5 score -
Average change from baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) score |
|
| 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 | No |
| 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) | 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 | No |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 157 |
| 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 | No |
| 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 |
| Argentina |
| Australia |
| Brazil |
| Bulgaria |
| Chile |
| Colombia |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Italy |
| Korea, Republic of |
| Mexico |
| New Zealand |
| Peru |
| Philippines |
| Romania |
| Russian Federation |
| Slovakia |
| South Africa |
| Spain |
| Sweden |
| Thailand |
| Ukraine |
| Vietnam |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
Print
