A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma

Phase 3

Completed

Conditions: Asthma

Interventions: Drug: budesonide/formoterol 'as needed' + budesonide placebo bid
Drug: budesonode bid + terbutaline 'as needed'

Registration Number: NCT02224157

Lead Sponsor: AstraZeneca

Brief Summary: The purpose of this study is to test if Symbicort (budesonide/formoterol) Turbuhaler is effective in treating asthma when used 'as needed' in patients with milder asthma. The efficacy of Symbicort 'as needed' will be compared with Pulmicort (budesonide) Turbuhaler twice daily plus terbutaline Turbuhaler 'as needed'

Detailed Description: A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group 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 Pulmicort (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg 'as needed'

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4215

Inclusion Criteria

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
Male or Female, ≥12 years of age
Documented diagnosis of asthma for at least 6 months prior to Visit 1
Patients who are in need of GINA step 2 treatment
Patients treated with a short acting inhaled bronchodilator(s) only should have pre-bronchodilator FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 % PN
Patients treated with low stable dose of ICS or leukotriene antagonists in addition to short acting inhaled bronchodilator(s) should have pre-bronchodilator FEV1 ≥80 % PN
Patients should have reversible airway obstruction
To be randomized patients must have used Bricanyl Turbuhaler as needed on at least 3 separate days during the last week of the run in period

Exclusion Criteria

Patient has a history of life-threatening asthma including intubation and intensive care unit admission
Patient has had an asthma worsening requiring change in treatment other than short acting inhaled bronchodilator(s) within 30 days prior to Visit 1 and from Visit 1 until randomization
Patient has required treatment with oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1
Current or previous smoker with a smoking history of ≥ 10 pack years
Pregnancy, breast-feeding or planned pregnancy during the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Symbicort "as needed"+placebo Pulmicort bid	budesonide/formoterol 'as needed' + budesonide placebo bid	Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid
Pulmicort bid + terbutaline "as needed"	budesonode bid + terbutaline 'as needed'	Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'

Primary Outcome Measures

Name	Time	Method
Annual Severe Asthma Exacerbation Rate - Superiority Analysis	up to 52 weeks	Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation
Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis	up to 52 weeks	Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation

Secondary Outcome Measures

Name	Time	Method
Average Change From Baseline in Pre-bronchodilator FEV1	Study weeks 0,17, 34, 52	The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
Average Change From Baseline in 'as Needed' Use	Week 0 up to 52 weeks	'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.
Number of Participants Experiencing at Least One Severe Asthma Exacerbation	Day 1 up to 52 weeks	A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.
Number of Participants With Study Specific Asthma Related Discontinuation	Day 1 up to 52 weeks	The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.
Change From Baseline in Percent of 'as Needed' Free Days	Week 0 up to 52 weeks	'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.
Percentage of Controller Use Days	Week 0 up to 52 weeks	ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.
Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score	Study weeks 0, 17, 34, 52	ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score	Study weeks 0,17, 34, 52	AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.