A 12-Week Study To Assess The Safety Of Fluticasone Propionate/Salmeterol 100/50 Hydrofluoroalkane (HFA) Versus Fluticasone Propionate 100 HFA In Children With Asthma

Study Overview
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Brief Summary
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This study is to assess the safety of an investigational drug in children 4 to 11 years of age who have asthma. The subjects will attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests performed.

Official Title
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A Randomized, Double-blind, Parallel Group Study Evaluating the Safety of Fluticasone Propionate/Salmeterol 100/50mcg HFA (2 Inhalations of 50/25mcg) Twice Daily Compared With Fluticasone Propionate 100mcg HFA (2 Inhalations of 50mcg) Twice Daily in Subjects 4-11 Years of Age With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: fluticasone propionate
* Drug: fluticasone propionate/salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Must have asthma. Must be currently taking an inhaled corticosteroid. Must be able to attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests that are at least 60% of normal (AM FEV1 or PEF). Have a historical or current FEV1 or PEF reversibility of >=12%. Exclusion criteria: Has ever had life-threatening asthma (for example respiratory arrest, mechanical ventilation). Has a current ear or respiratory tract infection. Has ever had any other major illnesses (such as cystic fibrosis, heart problems, tuberculosis).

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: Fluticasone propionate/salmeterol 100/50 HFA<br>Fluticasone propionate/salmeterol 100/50 HFA (2 inhalations of 50/25mcg), twice daily (strengths are ex-valve) and a placebo HFA inhaler matching the fluticasone propionate 100mcg HFA inhaler (2 inhalations) twice daily | Drug: fluticasone propionate/salmeterol<br>* fluticasone propionate/salmeterol 100/50mcg HFA<br>|
| Experimental: Fluticasone propionate 100mcg HFA<br>Fluticasone propionate 100mcg HFA (2 inhalations of 50mcg), twice daily (strengths are ex-valve) and a placebo HFA inhaler matching the fluticasone propionate/salmeterol 100/50 HFA inhaler (2 inhalations ) twice daily | Drug: fluticasone propionate<br>* fluticasone propionate 100mcg HFA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Possible Drug-Related Adverse Events | Adverse Events reported by the Investigator and judged by the Investigator to be possibly related to study drug, categorized by the Medical Dictionary for Regulatory Activities (MeDRA), were reported. ECG, electrocardiogram. QTc (corrected QT interval) and QT represent intervals on an ECG. | Treatment period (weeks 1-12) and Post Treatment (≥1 day after last time study drug) | 
| Investigator Evaluations of Electrocardiogram (ECG) Results | ECGs were transmitted to an independent cardiologist who was responsible for providing interpretation of the ECG as either normal or abnormal (based on personal assessment). The investigator was then responsible for determining the clinical significance of the abnormal ECG in the context of the participants' history and clinical presentation. An abnormal, clinically significant ECG included, but was not limited to: prolonged QT interval, ischemic changes, ventricular hypertrophy, intraventricular conduction abnormalities, and clinically significant arrhythmias. PD, premature discontinuation. | Baseline and Week 12 | 
| Clinically Significant Unfavorable ECGs at Week 12 | Post-randomization ECGs categorized by the primary investigator as no change, significant change (favorable), significant change (unfavorable) from the ECG performed at Visit 1 (Baseline) are presented. Significant change (favorable) includes any ECG that improved from baseline, whereas significant change (unfavorable) includes any ECG that worsened from baseline. Clinical significance is determined by the primary investigator. | Baseline, Week 12 | 
| ECG Measures - Heart Rate | The range of heart rates for this study was between 49-144 beats per minute | Baseline and Week 12 | 
| ECG Measures - QT Interval | Fridericia's formula QTc interval=QT interval/cubed root of the R-R interval. The Bazett's formula QTc=QT/squared root of the R-R interval. | Baseline and Week 12 | 
| Cardiovascular Adverse Events Reported During Treatment Period | Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Treatment Period. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event. Please see the category titles for a list of candidate cardiovascular adverse events. | 12-Week Treatment Period | 
| Cardiovascular Adverse Events Reported During the Post-Treatment Period | Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Post-treatment period, defined as 1 day after last dose of study drug. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event. | 5 Days after Week 12 | 
| Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | The Primary Investigator determined the severity of the exacerbation based on the participant's clinical presentation and the investigator's understanding of the disease, the participant, and his or her clinical experiences. The severity of the exacerbation was not defined in the protocol. Mild: Usually treated at home. Prompt relief with inhaled short-acting beta2 agonist. Possible short course of oral systemic corticosteroids. Moderate: Usually requires office or emergency department visit. Relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for 1-2 days after treatment begins. Severe: Usually requires emergency department visit and likely hospitalization. Partial relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for more than 3 days after treatment begins. Adjunctive therapies are helpful. | Treatment period (weeks 1-12) | 
| Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Abnormal high cortisol excretion and Abnormal low cortisol excretion are defined as above the upper limit of normal and below the lower limit of normal, respectively. The normal range for cortisol levels vary by age and gender. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory. | Baseline and week 12 | 
| Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Normal range for Cortisol levels vary by age and gender. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values. | Baseline and Week 12 | 
| Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion | Normal range for Cortisol levels vary by age and gender. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value, nanomoles per 24 hours (nmol/24 hrs). | Baseline and Week 12 | 
| Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. Abnormal high cortisol excretion and Abnormal low cortisol excretion are defined as above the upper limit of normal and below the lower limit of normal, respectively. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory. | Baseline and Week 12 | 
| Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values. | Baseline and Week 12 | 
| Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value, nanomoles per 24 hours (nmol/24 hrs). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | FEV1 (Forced Expiratory Volume in 1 second) is the volume of air that can be forced out in one second, after taking a deep breath. FEV1 is measured using a spirometer and obtaining best effort from 3 to 8 measurements. Week 12 is the measure taken at Week 12. | Baseline and week 12 | 
| AM Peak Expiratory Flow | The peak expiratory flow (PEF) rate measures how fast a person can exhale air. It is used to compare to normal flow rates to predict obstruction and disease. The average PEF for a child or adolescent whose height is 43 inches is 147 Liters/minute (L/min), whose height is 66 inches is 454 L/min. Triplicate measurements taken for the best effort recorded. | Baseline and 12-Week Treatment Period | 
| Asthma Symptom Scores | Each morning prior dosing or PEF, self-scored based on past 24 hours: 0=No symptoms, 1=Symptoms for one short period, 2=Symptoms for two or more short periods, 3=Frequent Symptoms which did not affect activities of daily living (ADL), 4=Frequent. | Baseline and 12-Week Treatment Period | 
| Percentage of Symptom Free Days | Percentage of number of days without asthma symptoms based on Asthma Symptom Scores. Each morning prior to dosing or PEF, asthma symptoms were self-scored based on the past 24 hours: 0=no symptoms, 1=symptoms for one short period, 2=symptoms for two or more short periods, 3=frequent symptoms that did not affect activities of daily living (ADL), 4=frequent . | Baseline and 12-Week Treatment Period | 
| Albuterol Use | Albuterol inhalation aerosol was used as a rescue or prophylactic and recorded daily by subject or caregiver. The number of puffs of albuterol over the previous 24 hour period prior to dosing was recorded. | Baseline and 12-Week Treatment Period | 
| Percent of Albuterol-free Days | Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days. | Baseline and 12-Week Treatment Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, fluticasone propionate, children, fluticasone propionate/salmeterol