SAS115359: A 6-month Study to Assess the Safety and Benefit of Inhaled Fluticasone Propionate/Salmeterol Combination Compared With Inhaled Fluticasone Propionate in the Treatment of Adolescents and Adults (12 Years of Age and Older) With Asthma.

Study Overview
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Brief Summary
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The purpose of this study is to assess whether the risk of serious asthma-related events (asthma-related hospitalizations, endotracheal intubations, and deaths) in adolescents and adults (12 years of age and older) taking inhaled fluticasone propionate/salmeterol combination is the same as those taking inhaled fluticasone propionate alone. ADVAIR™ and FLOVENT™ are trademarks of the GlaxoSmithKline Group of Companies.

Detailed Description
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Progress of Enrollment, Updated Annually: This study has been completed and the final clinical study report was submitted to the FDA in January of 2016. This is the final update, as this study is complete.

Official Title
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SAS115359, a Safety and Efficacy Study of Inhaled Fluticasone Propionate/Salmeterol Combination Versus Inhaled Fluticasone Propionate in the Treatment of Adolescent and Adult Subjects With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: ADVAIR 100/50mcg
* Drug: ADVAIR 250/50mcg
* Drug: ADVAIR 500/50mcg
* Drug: FLOVENT 100mcg
* Drug: FLOVENT 250mcg
* Drug: FLOVENT 500mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provided consent to participate in the study Male or female, 12 years of age and older Clinical diagnosis of asthma for at least 1 year prior to the randomization Clinic PEF of greater than or equal to 50% of predicted normal value Subject must be appropriately using one of the treatments for asthma listed in the protocol Subject must be able to complete the asthma control questionnaire, daily questions about asthma, and use a DISKUS inhaler Subject must have history of at least 1 asthma exacerbation including one of the following in the year prior to randomization: requiring treatment with systemic corticosteroids an asthma-related hospitalization Exclusion Criteria: History of life threatening asthma defined for this protocol as asthma episode that required intubation and/or was associated with hypercapnea requiring non-invasive ventilatory support Concurrent respiratory disease other than asthma Current evidence of, or ever been told by a physician that they have chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Exercise induced asthma (as the only asthma-related diagnosis) not requiring daily asthma control medicine Presence of a bacterial or viral respiratory infection that is not resolved at randomization An asthma exacerbation requiring systemic corticosteriods within 4 weeks of randomization or more than 4 separate exacerbations in the 12 months preceding randomization More than 2 hospitalizations for treatment of asthma in the 12 months preceding randomization Subject must not meet unstable asthma severity criteria as listed in the protocol Potent cytochrome P450 3A4 (CYP3A4) inhibitors within the last 4 weeks (e.g., ritonavir, ketoconazole, itraconzole) Pregnancy, breast-feeding or planned pregnancy during the study A Child in Care (CiC) is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADVAIR 100/50mcg<br>experimental drug | Drug: ADVAIR 100/50mcg<br>* fluticasone propionate/salmeterol combination (100/50mcg) twice daily (AM and PM) for 6 months<br>* Other names: FSC 100/50;|
| Experimental: ADVAIR 250/50mcg<br>experimental drug | Drug: ADVAIR 250/50mcg<br>* fluticasone propionate/salmeterol combination (250/50mcg) twice daily (AM and PM) for 6 months<br>* Other names: FSC 250/50;|
| Experimental: ADVAIR 500/50mcg<br>experimental drug | Drug: ADVAIR 500/50mcg<br>* fluticasone propionate/salmeterol combination (500/50mcg) twice daily (AM and PM) for 6 months<br>* Other names: FSC 500/50;|
| Active Comparator: FLOVENT 100mcg<br>active comparator | Drug: FLOVENT 100mcg<br>* fluticasone propionate (100) twice daily (AM and PM) for 6 months<br>* Other names: FP 100;|
| Active Comparator: FLOVENT 250mcg<br>active comparator | Drug: FLOVENT 250mcg<br>* fluticasone propionate (250mcg) twice daily (AM and PM) for 6 months<br>* Other names: FP 250;|
| Active Comparator: FLOVENT 500mcg<br>active comparator | Drug: FLOVENT 500mcg<br>* fluticasone propionate (500mcg) twice daily (AM and PM) for 6 months<br>* Other names: FP 500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Event in the Composite Safety Endpoint of Serious Asthma Outcomes ( Asthma-related Hospitalization, Asthma-related Endotracheal Intubation, or Asthma-related Death) | Composite endpoint was defined as clinically relevant endpoint that is constructed from combinations of other clinically relevant endpoints of serious asthma outcomes (i.e., asthma-related hospitalization, asthma-related endotracheal intubation, or asthma-related death). Hospitalization was defined as an inpatient stay or a ≥24-hour stay in an observation area in an emergency department or other equivalent facility. Probability of having event was summarized with Kaplan-Meier estimates.Hazard ratio, confidence interval, and p-value are from a stratified Cox proportional hazard model, using randomization stratum as the stratification factor. The 95% CI provided in the table is actually the 95. | From Day 1 up to 26 weeks | 
| Number of Participants Experiencing at Least One Asthma Exacerbation | An asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least three days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. | From Day 1 up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing at Least One Asthma Related Hospitalization , Endotracheal Intubation and Death | Hospitalization was defined as an inpatient stay or a ≥24-hour stay in an observation area in an emergency department or other equivalent facility. | From Day 1 up to 26 weeks | 
| Number of Participant Withdrawals From Study Treatment Due to Asthma Exacerbation | An asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least three days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. | From Day 1 up to 26 weeks | 
| Mean Rescue Medication (Albuterol/Salbutamol) Use as Puffs Per 24 Hours | Rescue medication included albuterol/salbutamol used to treat acute asthma were reported as puffs per 24 hours over a period of 6 months. | From Day 1 up to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADVAIR, Asthma, safety, FLOVENT