New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day

Study Overview
=================
Brief Summary
-----------------
This is a comparison of the efficacy of the Symbicort breath actuated dose inhaler to the Symbicort pressured meter dose inhaler after 12 weeks of a twice a day dose.

Official Title
-----------------
A 12-week, Double-blind, Randomized, Multi-centre, Parallel-group Study Evaluating the Efficacy Safety, and Patient Use (User Study) of Symbicort® (Budesonide/Formoterol) Breath Actuated Metered Dose Inhaler (BA MDI) 2x160/4.5 μg Twice Daily Compared With Symbicort (Budesonide/Formoterol) AC (Actuation Counter) pMDI® 2x160/4.5 μg Twice Daily and Budesonide AC pMDI 2x160 μg Twice Daily in Adult and Adolescent Asthmatics

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Symbicort
* Drug: Symbicort
* Drug: Budesonide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female 12 years and above Clinical diagnosis of asthma according to the American Thoracic Society definition at least 6 months Pre-bronchodilator FEV1 ≥ 45% and ≤ 85% of predicted normal Patients with reversible airway obstruction Documented daily use of inhaled corticosteroids for ≥ 3 months Exclusion Criteria: History of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures during the 2 years prior to Visit 2 Hospitalized during previous 6 months for asthma Required emergency treatment more than once during previous 6 months for an asthma-related condition Intake of oral, rectal or parenteral glucocorticosteroid within 30 days of enrolment Respiratory infection affecting the asthma within 30 days

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Symbicort/inhaler<br>Symbicort BA MDI 2x160/4.5 μg twice daily | Drug: Symbicort<br>* Breath actuated metered dose inhaler<br>|
| Active Comparator: Symbicort/inhaler<br>Symbicort AC pDMI 2x160/4.5 μg twice daily | Drug: Symbicort<br>* Actuation counter pressured metered dose inhaler<br>|
| Active Comparator: Budesonide/inhaler<br>Budesonide AC pMDI 2x160 μg twice daily | Drug: Budesonide<br>* Actuation counter pressured metered dose inhaler<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) - Post Dose | Descriptive statistics for post-dose FEV1 (L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization. | 60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg | 
| Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose | Descriptive statistics for predose FEV1(L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization. | Pre AM dose in clinic visits at baseline, and week 3, 7, 12 and Trt Avg | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Expiratory Flow |  | Recorded morning upon rising and evening before sleep for 14 weeks | 
| Asthma Symptoms Score (Total) | The total score is calculated as sum of the morning and evening scores of each day and the treatment period mean score is defined as the mean of all total score recorded during the 12-week treatment period. Trt Avg=Mean total score of double-blind period values.(day/night score ranges from 0 to 3; 0=no asthma symptoms; 3= unable to do normal activities (or to sleep) due to asthma). Higher score represents worse outcome. | Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks | 
| Night-time Awakenings Due to Asthma Symptoms(% Awakening-free Nights) | The percentage of days with no awakenings due to asthma. Baseline= Mean % awakening-free nights during run-in period ; Trt Avg=Mean % awakening-free nights during double-blind period. | Recorded 6:00 - 11:00 AM for 14 weeks | 
| Use of Rescue Medication Day and Night (Total Daily Rescue Medication Use) | Total daily rescue medication use is calculated as the sum of morning and evening use each day and averaged over the 12 weeks treatment periods to calculate the treatment period mean. Baseline= Mean rescue medication used during run-in period ; Trt Avg=Mean rescue medication used during double-blind period. | Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks |