Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX® Inhalation Powder Versus SYMBICORT® TURBOHALER®

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to establish whether budesonide/formoterol fumarate dihydrate (BF) Spiromax 160/4.5 micrograms (mcg) is as effective as Symbicort Turbohaler 200/6 mcg administered twice daily in participants with persistent asthma.

Official Title
-----------------
A 12-Week Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX(R) 160/4.5 mcg Inhalation Powder Versus SYMBICORT(R) TURBOHALER(R) 200/6 mcg in Adult and Adolescent Patients With Persistent Asthma

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

Intervention / Treatment
-----------------
* Drug: Budesonide/Formoterol SPIROMAX®
* Drug: SYMBICORT® TURBOHALER®
* Drug: SYMBICORT placebo
* Drug: SPIROMAX Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants 12 years and older as of the screening visit. Male or female participants 18 years and older, as of the screening visit, in countries where local regulations or the regulatory status of study medication permit enrollment of adult participants only. General good health, and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the participant at increased risk during the study. Asthma Diagnosis: The asthma diagnosis must be in accordance with the Global Initiative for Asthma (GINA) Exclusion Criteria: History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures. Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks before the screening visit. In addition, the participant must be excluded if such infection occurs between the screening visit and the baseline visit. Any asthma exacerbation requiring oral corticosteroids within 1 month of the screening visit. A participant must not have been hospitalized for asthma within 6 months before the screening visit. Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular conditions (for example, congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine conditions (for example, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison's disease, Cushing's syndrome), gastrointestinal conditions (for example, poorly-controlled peptic ulcer, gastroesophageal reflux disease [GERD]), or pulmonary conditions (for example, chronic bronchitis, emphysema, bronchiectasis with the need for treatment, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition became exacerbated during the study. NOTE: Other inclusion and exclusion criteria may apply.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BF Spiromax<br>2 inhalations of BF Spiromax at a dosage of 160/4.5 mcg and 2 inhalations of SYMBICORT placebo administered twice daily (AM and PM) during the 12-week treatment period. | Drug: Budesonide/Formoterol SPIROMAX®<br>* BF Spiromax will be administered per dose and schedule specified in the arm.<br>Drug: SYMBICORT placebo<br>* SYMBICORT placebo multi-dose dry powder inhaler (DPI) identical in appearance to SYMBICORT TURBOHALER will be administered per dose and schedule specified in the arm.<br>|
| Active Comparator: Symbicort Turbohaler<br>2 inhalations of SYMBICORT TURBOHALER at a dosage of 200/6 mcg and 2 inhalations of placebo SPIROMAX administered twice daily (AM and PM) during the 12-week treatment period. | Drug: SYMBICORT® TURBOHALER®<br>* Symbicort Turbohaler will be administered per dose and schedule specified in the arm.<br>Drug: SPIROMAX Placebo<br>* SPIROMAX Placebo multi-dose dry powder inhaler (DPI) identical in appearance to BF SPIROMAX will be administered per dose and schedule specified in the arm.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Average of Daily Trough (Predose and Pre-rescue Bronchodilator) Morning (AM) Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period | PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. | Baseline, Weeks 1 to 12 (averaged over 12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period | PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline was defined as the average value of the recorded (nonmissing) assessments over the 7 days prior to randomization. For postdose weekly average of evening PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of evening PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. | Baseline, Weeks 1 to 12 (averaged over 12 weeks) | 
| Number of Participants With Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. | Baseline up to Week 12 | 
| Number of Participants With Signs of Oral Candidiasis (Thrush) | Examinations were performed by a qualified professional. | Baseline, Week 4, Week 8, Week 12 | 
| Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Swab samples were collected by a qualified professional. | Baseline, Week 4, Week 8, Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Budesonide/Formoterol SPIROMAX®, SYMBICORT® TURBOHALER®, Asthma