6-month Safety and Benefit Study of ADVAIR in Children 4-11 Years Old

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 children 4-11 years old taking inhaled fluticasone propionate/salmeterol combination is the same as those taking inhaled fluticasone propionate alone.

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 May of 2016. This is the final update, as this study is complete.

Official Title
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A 6-month Safety and Benefit Study of Inhaled Fluticasone Propionate/ Salmeterol Combination Versus Inhaled Fluticasone Propionate in the Treatment of 6,200 Pediatric Subjects 4-11 Years Old With Persistent Asthma

Conditions
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Asthma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent to participate in the study Age 4-11 years old Male or eligible female - Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation Asthma diagnosis for at least 6 months Ability to answer questions regarding asthma control and use a metered dose inhaler and DISKUS A history of clinical varicella infection or recipient of a varicella vaccine in countries where the product label includes a warning regarding more serious chickenpox infections in patients using corticosteroids. History of at least once occurrence of asthma exacerbation within the prior 12 months Currently being treated for asthma and no change in asthma therapy for the last 4 weeks (Eligible subjects include: subjects with use of short-acting beta-agonist, leukotriene receptor antagonist, theophylline, or cromolyn whose asthma is not well-controlled; subjects on low-dose ICS monotherapy whose asthma is not well-controlled; subjects on low-dose ICS and one or more adjunctive therapy whose asthma is either controlled or not well-controlled asthma; subjects on medium-dose ICS monotherapy whose asthma is either controlled or not well-controlled; and subjects on medium-dose ICS and one or more adjunctive therapy whose asthma is well-controlled) Exclusion Criteria: History of life-threatening asthma Unstable asthma Current use of high-dose ICS or ICS/LABA therapy to treat asthma symptoms Concurrent respiratory disease: Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, or other severe respiratory abnormalities other than asthma. Respiratory infection Subjects with only exercise-induced asthma An asthma exacerbation within the last 4 weeks or more than 4 separate exacerbations in the last 12 months Hospitalization for asthma within 4 weeks or more than 2 hospitalizations within the last 12 months Other current evidence of clinically significant uncontrolled disease/conditions of any body or organ system Neurological or psychiatric disease or history of drug or alcohol abuse of a subject or his/her guardian which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirements Participation in an interventional study or used any investigational drug for any disease state within the last 30 days Any adverse reaction including immediate or delayed hypersensitivity to any beta-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy, or vehicle contained within these medication Severe hypersensitivity to cow's milk proteins Administration of prescription or over the counter medications that would significantly affect the course of asthma, or interact with sympathomimetic amines such as: anti-IgE (omalizumab), anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants, beta-adrenergic blockers; phenothiazines, monoamine oxidase inhibitors, or diuretics Potent cytochrome P450 3A4 (CYP3A4) inhibitors within the last 4 weeks (e.g., ritonavir, ketoconazole, itraconzole) Affiliation with investigator's site, including a immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator. 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: 4 Years
Maximum Age: 11 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: Quadruple


Arms and Interventions

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

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. Time to first event in the composite endpoint of serious asthma-related outcomes over the 6-month study treatment period was analyzed using a Cox proportional hazards regression model. An estimate of absolute risk difference and its corresponding 95% confidence interval (CI) were also included. The Intent-to-Treat (ITT) Population included all participants randomized to study drug and who took study treatment. | From Day 1 up to 6 months | 
| Number of Participants With at Least One Asthma Exacerbation Over the 6-month Study Treatment Period | Number of participants with asthma exacerbation over the 6-month study treatment period are presented. Participants from mITT population with screening childhood asthma control test (C-ACT) scores of 20 or higher, one exacerbation in the previous year, and either low-dose inhaled corticosteroid (ICS) + one or more adjunctive therapy or medium-dose ICS monotherapy or medium-dose ICS and one or more adjunctive therapy as prior asthma therapy were included for this endpoint. Time to first exacerbation analyzed using a cox proportional hazards regression model. The number of asthma exacerbations were compared between treatments using a negative binomial regression model. The modified Intent-to-Treat (mITT) Population consisted of the ITT participants with a different data cut-off for supportive analyses of the primary composite safety endpoint. | From Day 1 up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Asthma-related Deaths Over the 6-month Study Treatment Period. | Number of participants experiencing asthma-related death over the 6-month study treatment period are presented. | From Day 1 up to 6 months | 
| Number of Participants Experiencing Asthma-related Endotracheal Intubations Over the 6-month Study Treatment Period | Intubation is defined as endotracheal intubation with ventilation (mechanical or by hand). The number of participants experiencing asthma-related endotracheal intubations over the 6-month study treatment period are presented. | From Day 1 up to 6 months | 
| Number of Participants Experiencing Asthma-related Hospitalizations Over the 6-month Study Treatment Period | Hospitalization is defined as a >=24-hour stay as an inpatient or in an observation ward. The number of participants experiencing asthma-related hospitalizations over the 6-month study treatment period are presented. | From Day 1 up to 6 months | 
| Number of Participants Withdrawn From Study Treatment Due to Asthma Exacerbation Over the 6-month Study Treatment Period | An exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days (up to 10 days) or a single depot corticosteroid injection. Number of participants experiencing at least one exacerbation from mITT population were included for this endpoint. The number of participants withdrawn from study treatment due to asthma exacerbation over the 6-month study treatment period are presented. | From Day 1 up to 6 months | 
| Percentage of Rescue-free Days Over the 6-month Study Treatment Period | Rescue-free days were days without use of rescue albuterol/salbutamol (other than pre-exercise treatment) over the 6-month study treatment period. The mean percentages of rescue-free days over the months 1-6 (defined as treatment days 2-182) are summarized. Number of participants over treatment days 2-182 from mITT Population were included for this endpoint. | From Day 1 up to 6 months | 
| Percentage of Asthma Control Days Over the 6-month Study Treatment Period | An asthma control day is one on which rescue albuterol/salbutamol use was recorded as 0, no night time awakenings were recorded, no asthma exacerbations were recorded, no work, school, or daycare days were missed by caregiver or participant due to asthma, coughing symptom score was <=1 and wheezing symptom score was 0. The mean percentages of asthma control days over the months 1-6 (defined as treatment days 2-182) are summarized. Number of participants over treatment days 2-182 from mITT Population were included for this endpoint. | From Day 1 up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, ADVAIR, FLOVENT, asthma