A 52-week, double-blind, randomised, multi-centre, parallel-group,Phase III study in patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort® (budesonide/formoterol) Turbuhaler® 160/4.5 µg ‘as needed’ compared with terbutaline Turbuhaler® 0.4 mg ‘as needed’ and with Pulmicort® (budesonide) Turbuhaler® 200 µg twice daily plus terbutaline Turbuhaler® 0.4 mg ‘as needed’
- Conditions
- AsthmaTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2013-004474-96-RO
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 3836
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 for GINA step 2 treatment:
-uncontrolled on SABA ‘as needed’ 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, or LTRAs as judged by the investigator for the last 30 days prior to Visit 2
5.Based on lung function tests at Visit 2, patients pre-treated with
-a SABA only should have prebronchodilator FEV1 = 60 % of predicted normal (PN) and postbronchodilator FEV1 = 80 % PN according to the European Respiratory Society (ERS) guidelines
-low dose ICS or LTRAs medication should have prebronchodilator FEV1 =80 % PN according to the ERS guidelines
6.Reversible airway obstruction according to a reversibility test performed at Visit 2 defined as an increase in FEV1 =12% and 200 ml relative to baseline, 15-30 minutes 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 on low dose ICS or LTRAs 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 ß2-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 recorded for at least 8 days (any 8) of the last 10 days of the run-in period.
Are the trial subjects under 18? yes
Number of subjects for this age range: 375
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3375
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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 enrolment 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 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 ß-blocking agent including eye-drops
8.Known or suspected hypersensitivity to study drugs or excipient
9.Current or previous smoker with a smoking history of = 10 pack years
10.Medical history of life- threatening asthma including intubation and intensive care unit submission
11.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, 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 on more than 2 days during the run-in period
17.Any asthma worsening requiring change in treatment other than SABA from Visit 1 until randomization
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate that Symbicort Turbuhaler 160/4.5 µg ‘as needed’ is superior to terbutaline Turbuhaler 0.4 mg ‘as needed’.;Secondary Objective: 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’.<br>2.To evaluate the efficacy of Symbicort Turbuhaler 160/4.5 µg as compared to both:<br>terbutaline Turbuhaler 0.4 mg ‘as needed’<br>And:<br>Pulmicort Turbuhaler 200 µg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.<br>;Primary end point(s): Evaluation of asthma control as measured by well-controlled asthma weeks as the primary variable;Timepoint(s) of evaluation of this end point: well-controlled asthma weeks, weekly, up to 52 weeks
- Secondary Outcome Measures
Name Time Method