| 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 superior to terbutaline Turbuhaler 0.4 mg ‘as needed’. |
|
| E.2.2 | Secondary objectives of the trial |
1.To evaluate the relative efficacy of Symbicort Turbuhaler 160/4.5 μg ‘as needed’ and Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
2.To evaluate the efficacy of Symbicort Turbuhaler 160/4.5 μg as compared to both:
terbutaline Turbuhaler 0.4 mg ‘as needed’
And:
Pulmicort Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Sub-study with Qualitative Interviews
Date: 2016-02-24
Sub-study objectives: The objective of this sub-study is to understand patient usage of study inhalers during the clinical study (particularly when and why study inhalers are used) from a qualitative patient centred perspective.
The additional objectives are to:
- Understand the patient experience of asthma control during the clinical study
- Understand whether or not patients believe their asthma control has changed during their participation in the clinical study
- Understand what the term “asthma control” means to the patient
|
|
| E.3 | Principal inclusion criteria |
For inclusion in the study patients should fulfil the following 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 based on symptoms with a
documented history of at least 6 months prior to Visit 1. Lung function and
reversibility tests performed as part of Visit 2 and 3 can be used as a confirmation
of asthma diagnosis according to GINA criteria if there is no measure of lung
function available before Visit 1.
4. Patients who are in need of GINA (2012) step 2 treatment:
- uncontrolled on inhaled short-acting bronchodilator(s) ‘as needed’ (SABA
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(s) (SABA 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
an inhaled short acting bronchodilator only should have pre-bronchodilator
FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 %
PN according to the European Respiratory Society (ERS) guidelines (Quanjer
et al 2012)
- low dose ICS or LTRA medication in addition to inhaled short-acting
bronchodilator(s) 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 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 and to complete the eDiary correctly. Morning
and evening data must be |
|
| E.4 | Principal exclusion criteria |
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
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
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 inhaled
short-acting bronchodilator(s) (SABA and/or short acting anticholinergic agent)
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 asthma treatment other than inhaled
short-acting bronchodilator(s) (SABA and/or short acting anticholinergic agent)
from Visit 1 until Visit 2 and/or requiring any asthma treatment other than run-in
study medication from Visit 2 until randomisation |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Evaluation of asthma control as measured by well-controlled asthma weeks as the primary variable |
|
| 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
Time to first moderate or severe asthma exacerbation
Average change from baseline in pre-dose FEV1
Average change from baseline in Morning PEF
Average change from baseline in Evening PEF
Average change from baseline in number of inhalations of ‘as needed’ medication
Average change from baseline in symptom score
Percentage of Nighttime awakenings due to asthma
Percentage of Symptom-free days
Percentage of ‘As needed’ free days
Percentage of Asthma control days
Time to asthma related discontinuation
Poorly controlled asthma weeks
Time to additional steroids for asthma
Average change from baseline in Asthma Control Questionnaire (ACQ-5)
Average change from baseline in Asthma Quality of Life Questionnaire; standard version (AQLQ(S))
|
|
| 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 | 3 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 123 |
| 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 |
| Canada |
| Chile |
| China |
| Hungary |
| Korea, Republic of |
| Mexico |
| Peru |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| South Africa |
| Ukraine |
| United Kingdom |
| 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 | 8 |
| 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 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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