A Safety and Efficacy Study of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) or Metered-Dose Inhaler (MDI) in Participants Ages 4-11 Years Old With Persistent Asthma

Study Overview
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Brief Summary
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This randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study will evaluate the efficacy and safety of beclomethasone dipropionate (80 or 160 mcg/day) administered via breath-actuated inhaler (BAI) and metered-dose inhaler (MDI) in pediatric patients 4 through 11 years of age with persistent asthma, compared with placebo. Patients took 1 inhalation (with assistance from parents/guardians/caregivers, as needed) from each of 2 devices (BAI device followed by MDI device in that order) twice daily as per the double-dummy study design: 1 BAI treatment or placebo device and 1 MDI treatment or placebo device for a total of 2 inhalations each time.

Official Title
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, 12-Week Clinical Study to Assess the Efficacy and Safety of 80 or 160 mcg/Day of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) or Metered-Dose Inhaler (MDI) in Pediatric Patients 4 Through 11 Years of Age With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Beclomethasone dipropionate BAI
* Drug: Placebo BAI
* Drug: albuterol/salbutamol 90 mcg
* Drug: Beclomethasone dipropionate MDI
* Drug: Placebo MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National Institute of Health (NIH). The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in medication) for at least 30 days before screening visit Severity of disease: The patient has persistent asthma, with a forced expiratory volume in 1 second (FEV1) 40% to 90% of the value predicted for age, height, and sex at screening visit (SV) Current asthma therapy: The patient is currently being treated with 1 of the following: 1) a stable daily dosage of an inhaled corticosteroid (ICS) in the range of 88-176 mcg/day of fluticasone propionate (or equivalent) for a minimum of 4 weeks (28 days) before screening visit 2) a stable daily dosage of non-corticosteroid therapy 3) a daily dose of ICS plus a long-acting beta2-agonist (LABA) (at a dose less than or equivalent to fluticasone propionate 100 mcg/salmeterol 50 mcg twice daily) Reversibility of disease: The patient has demonstrated at least 12% reversibility of FEV1 within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at screening visit or on retesting. Other criteria apply, please contact the investigator for more information Exclusion Criteria: The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures. The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the patient's last study-related visit (for eligible patients only, if applicable). Any patient becoming pregnant during the study will be withdrawn from the study. The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation. The patient has used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco, as applicable). The patient has had an asthma exacerbation requiring oral corticosteroids within 30 days before screening visit, or has had any hospitalization for asthma within 2 months before screening visit. The patient has historical or current evidence of a clinically significant disease. Significant disease is defined as any disease that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study. Other criteria apply, please contact the investigator for more information

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BDP 80 mcg BAI<br>Beclomethasone dipropionate (BDP) was administered via a breath-actuated inhaler (BAI) twice daily (40 mcg twice a day). Placebo MDI twice daily for blinding. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | Drug: Beclomethasone dipropionate BAI<br>* Beclomethasone dipropionate (BDP), was delivered by a single inhalation using a breath-actuated inhaler (BAI) at levels of 40 mcg or 80 mcg per inhalation, twice each day.<br>* Other names: breath-actuated inhaler;Drug: albuterol/salbutamol 90 mcg<br>* Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.<br>* Other names: bronchodilators;Drug: Placebo MDI<br>* Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.<br>|
| Experimental: BDP 160 mcg BAI<br>Beclomethasone dipropionate (BDP) was administered via a breath-actuated inhaler (BAI) twice daily (80 mcg twice a day). Placebo MDI twice daily for blinding. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | Drug: Beclomethasone dipropionate BAI<br>* Beclomethasone dipropionate (BDP), was delivered by a single inhalation using a breath-actuated inhaler (BAI) at levels of 40 mcg or 80 mcg per inhalation, twice each day.<br>* Other names: breath-actuated inhaler;Drug: albuterol/salbutamol 90 mcg<br>* Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.<br>* Other names: bronchodilators;Drug: Placebo MDI<br>* Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.<br>|
| Active Comparator: BDP 80 mcg MDI<br>Beclomethasone dipropionate (BDP) was administered via a metered-dose inhaler (MDI) twice daily (40 mcg twice a day). Placebo BAI twice daily for blinding. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | Drug: Placebo BAI<br>* Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.<br>* Other names: breath-actuated inhaler;Drug: albuterol/salbutamol 90 mcg<br>* Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.<br>* Other names: bronchodilators;Drug: Beclomethasone dipropionate MDI<br>* Beclomethasone dipropionate (BDP), was delivered by a single inhalation using a metered-dose inhaler (MDI) at levels of 40 mcg or 80 mcg per inhalation, twice each day.<br>* Other names: QVAR®;|
| Active Comparator: BDP 160 mcg MDI<br>Beclomethasone dipropionate (BDP) was administered via a metered-dose inhaler (MDI) twice daily (80 mcg twice a day). Placebo BAI twice daily for blinding. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | Drug: Placebo BAI<br>* Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.<br>* Other names: breath-actuated inhaler;Drug: albuterol/salbutamol 90 mcg<br>* Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.<br>* Other names: bronchodilators;Drug: Beclomethasone dipropionate MDI<br>* Beclomethasone dipropionate (BDP), was delivered by a single inhalation using a metered-dose inhaler (MDI) at levels of 40 mcg or 80 mcg per inhalation, twice each day.<br>* Other names: QVAR®;|
| Placebo Comparator: Placebo BAI and MDI<br>Placebo was administered via breath-actuated inhaler (BAI) twice daily. Additionally placebo was administered via metered-dose inhaler (MDI) twice daily. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | Drug: Placebo BAI<br>* Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.<br>* Other names: breath-actuated inhaler;Drug: albuterol/salbutamol 90 mcg<br>* Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI [90 mcg ex-actuator] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period.<br>* Other names: bronchodilators;Drug: Placebo MDI<br>* Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Baseline-adjusted Trough Morning Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time 0 to 12 Weeks (AUEC(0-12wk)) | Trough morning FEV1 measurements were taken pre-dose and pre-rescue bronchodilator treatment for asthma. Baseline was defined as baseline trough morning percent predicted FEV1. Pulmonary function measurements (including FEV1) were obtained electronically by spirometry. All pulmonary function test data were submitted to a central reading center for evaluation. The highest ('best attempt') FEV1 value from 3 acceptable and 2 repeatable maneuvers (maximum of 8 attempts) was used. | Day 1 (baseline), Weeks 2, 4, 8, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period | The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF calculated across the 12-week treatment period was performed using a mixed model for repeated measures (MMRM) with effects due to baseline weekly average of daily trough morning PEF. | Day 1 (baseline), weeks 1-12 | 
| Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-week Treatment Period | The analysis of change from baseline in the weekly average of daily evening PEF across the 12-week treatment period was performed using a mixed model for repeated measures (MMRM) with effects due to baseline weekly average of daily evening PEF. | Day 1 (baseline), weeks 1-12 | 
| Change From Baseline in the Weekly Average of Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1-12 | The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) across the 12 weeks was analyzed using a mixed model for repeated measures (MMRM). | Day 1 (baseline), weeks 1-12 | 
| Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12 | The total daily asthma symptom score is the average of the daytime and nighttime scores analyzed using an mixed model for repeated measures (MMRM). Baseline was defined as the average of recorded morning and evening asthma symptom scores over the 7 days before randomization. Daytime Scores range from 0=No symptoms during the day to 5=Symptoms so severe that I could not go to work or perform normal daily activities; Nighttime Scores range from 0=No symptoms during the night to 4=Symptoms so severe that I did not sleep at all. The daily asthma symptom score was therefore 0 - 9 with 0=no symptoms during the day or night and 9=severe symptoms both day and night. | Day 1 (baseline), weeks 1-12 | 
| Kaplan-Meier Estimates For Time to Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-week Treatment Period | Time to withdrawal due to meeting stopping criteria was defined as number of days elapsed from the date of first dose of double-blind study treatment to the date of withdrawal due to meeting stopping criteria. Kaplan-Meier estimates (median and 95% CI of the median) are not applicable if the proportion of participants withdrawn is less than 0.5. | Day 1 to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, breath-actuated inhaler, metered dose inhaler