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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Beclomethasone dipropionate BAI; Drug: albuterol/salbutamol 90 mcg; Drug: Placebo MDI; Drug: Placebo BAI; Drug: Beclomethasone dipropionate MDI

• Study Type: Interventional
• Enrollment (Actual): 628
• Phase: Phase 3

Contacts and Locations

Study Locations

• Croatia
  • Cakovec, Croatia
    • Teva Investigational Site 60017
  • Zagreb, Croatia
    • Teva Investigational Site 60018
  • Zagreb, Croatia
    • Teva Investigational Site 60019
• Mexico
  • Guadalajara, Mexico
    • Teva Investigational Site 21037
  • Guadalajara, Mexico
    • Teva Investigational Site 21042
  • Mexico City, Mexico
    • Teva Investigational Site 21039
  • Mexico City, Mexico
    • Teva Investigational Site 21045
  • Monterrey, Mexico
    • Teva Investigational Site 21035
  • San Lucas Tepetlacalco, Mexico
    • Teva Investigational Site 21043
  • San Lucas Tepetlacalco, Mexico
    • Teva Investigational Site 21047
  • Zapopan, Mexico
    • Teva Investigational Site 21051
• Poland
  • Bialystok, Poland
    • Teva Investigational Site 53276
  • Krakow, Poland
    • Teva Investigational Site 53267
  • Lodz, Poland
    • Teva Investigational Site 53269
  • Lodz, Poland
    • Teva Investigational Site 53272
  • Lublin, Poland
    • Teva Investigational Site 53271
  • Lublin, Poland
    • Teva Investigational Site 53274
  • Tarnow, Poland
    • Teva Investigational Site 53273
  • Wroclaw, Poland
    • Teva Investigational Site 53275
  • Zawadzkie, Poland
    • Teva Investigational Site 53270
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Teva Investigational Site 58165
  • Kharkiv, Ukraine
    • Teva Investigational Site 58171
  • Kryvyi Rih, Ukraine
    • Teva Investigational Site 58168
  • Kyiv, Ukraine
    • Teva Investigational Site 58167
  • Kyiv, Ukraine
    • Teva Investigational Site 58172
  • Zaporizhzhia, Ukraine
    • Teva Investigational Site 58169
  • Zaporizhzhya, Ukraine
    • Teva Investigational Site 58170
• United States
  • Alabama
    • Hoover, Alabama, United States
      • Teva Investigational Site 12346
    • Montgomery, Alabama, United States
      • Teva Investigational Site 12294
  • Arizona
    • Phoenix, Arizona, United States
      • Teva Investigational Site 10925
  • Arkansas
    • Little Rock, Arkansas, United States
      • Teva Investigational Site 12349
  • California
    • Costa Mesa, California, United States
      • Teva Investigational Site 10903
    • Downey, California, United States
      • Teva Investigational Site 10911
    • Huntington Beach, California, United States
      • Teva Investigational Site 10901
    • Huntington Beach, California, United States
      • Teva Investigational Site 12297
    • Mission Viejo, California, United States
      • Teva Investigational Site 10880
    • Orange, California, United States
      • Teva Investigational Site 10895
    • Paramount, California, United States
      • Teva Investigational Site 10924
    • Rolling Hills Estates, California, United States
      • Teva Investigational Site 10910
    • Roseville, California, United States
      • Teva Investigational Site 12343
    • San Diego, California, United States
      • Teva Investigational Site 12298
    • San Diego, California, United States
      • Teva Investigational Site 12300
    • San Jose, California, United States
      • Teva Investigational Site 12295
    • West Covina, California, United States
      • Teva Investigational Site 12312
  • Colorado
    • Centennial, Colorado, United States
      • Teva Investigational Site 10937
    • Colorado Springs, Colorado, United States
      • Teva Investigational Site 10899
  • Florida
    • Aventura, Florida, United States
      • Teva Investigational Site 10894
    • Gainesville, Florida, United States
      • Teva Investigational Site 12335
    • Homestead, Florida, United States
      • Teva Investigational Site 12336
    • Homestead, Florida, United States
      • Teva Investigational Site 12345
    • Miami, Florida, United States
      • Teva Investigational Site 12315
    • Miami, Florida, United States
      • Teva Investigational Site 12341
    • Miami, Florida, United States
      • Teva Investigational Site 12342
    • Orlando, Florida, United States
      • Teva Investigational Site 10919
    • Sarasota, Florida, United States
      • Teva Investigational Site 12281
    • Winter Park, Florida, United States
      • Teva Investigational Site 12332
  • Georgia
    • Gainesville, Georgia, United States
      • Teva Investigational Site 10935
    • Lawrenceville, Georgia, United States
      • Teva Investigational Site 10912
    • Savannah, Georgia, United States
      • Teva Investigational Site 10927
  • Kentucky
    • Owensboro, Kentucky, United States
      • Teva Investigational Site 10885
  • Louisiana
    • Covington, Louisiana, United States
      • Teva Investigational Site 12317
  • Maryland
    • Baltimore, Maryland, United States
      • Teva Investigational Site 12296
    • White Marsh, Maryland, United States
      • Teva Investigational Site 12323
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • Teva Investigational Site 10897
  • Michigan
    • Ypsilanti, Michigan, United States
      • Teva Investigational Site 10932
  • Minnesota
    • Plymouth, Minnesota, United States
      • Teva Investigational Site 10914
  • Missouri
    • Columbia, Missouri, United States
      • Teva Investigational Site 10917
    • Rolla, Missouri, United States
      • Teva Investigational Site 10916
  • Montana
    • Missoula, Montana, United States
      • Teva Investigational Site 12331
  • New Jersey
    • Brick, New Jersey, United States
      • Teva Investigational Site 10922
    • Ocean City, New Jersey, United States
      • Teva Investigational Site 10909
    • Verona, New Jersey, United States
      • Teva Investigational Site 12289
  • North Carolina
    • Asheville, North Carolina, United States
      • Teva Investigational Site 10939
    • Charlotte, North Carolina, United States
      • Teva Investigational Site 12348
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 10893
  • Ohio
    • Canton, Ohio, United States
      • Teva Investigational Site 10888
    • Fairfield, Ohio, United States
      • Teva Investigational Site 12302
    • Toledo, Ohio, United States
      • Teva Investigational Site 10921
    • Toledo, Ohio, United States
      • Teva Investigational Site 12285
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 10906
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 10915
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 12314
    • Tulsa, Oklahoma, United States
      • Teva Investigational Site 10891
  • Oregon
    • Medford, Oregon, United States
      • Teva Investigational Site 10892
    • Portland, Oregon, United States
      • Teva Investigational Site 10898
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Teva Investigational Site 12273
  • Rhode Island
    • Warwick, Rhode Island, United States
      • Teva Investigational Site 12282
  • South Carolina
    • North Charleston, South Carolina, United States
      • Teva Investigational Site 10902
    • Orangeburg, South Carolina, United States
      • Teva Investigational Site 10938
  • Texas
    • Beaumont, Texas, United States
      • Teva Investigational Site 12347
    • Boerne, Texas, United States
      • Teva Investigational Site 10926
    • Dallas, Texas, United States
      • Teva Investigational Site 10908
    • Dallas, Texas, United States
      • Teva Investigational Site 10918
    • El Paso, Texas, United States
      • Teva Investigational Site 12291
    • Live Oak, Texas, United States
      • Teva Investigational Site 12329
    • New Braunfels, Texas, United States
      • Teva Investigational Site 10890
    • San Antonio, Texas, United States
      • Teva Investigational Site 10904
    • San Antonio, Texas, United States
      • Teva Investigational Site 10929
    • Waco, Texas, United States
      • Teva Investigational Site 10879
  • Virginia
    • Richmond, Virginia, United States
      • Teva Investigational Site 10883
  • Washington
    • Bellingham, Washington, United States
      • Teva Investigational Site 10886
  • Wisconsin
    • Greenfield, Wisconsin, United States
      • Teva Investigational Site 10913

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BDP 80 mcg BAI; 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; 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.; Other Names: BDP; breath-actuated inhaler; Drug: albuterol/salbutamol 90 mcg; 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.; Other Names: bronchodilators; Drug: Placebo MDI; Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.
EXPERIMENTAL: BDP 160 mcg BAI; 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; 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.; Other Names: BDP; breath-actuated inhaler; Drug: albuterol/salbutamol 90 mcg; 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.; Other Names: bronchodilators; Drug: Placebo MDI; Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.
ACTIVE_COMPARATOR: BDP 80 mcg MDI; 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: albuterol/salbutamol 90 mcg; 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.; Other Names: bronchodilators; Drug: Placebo BAI; Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.; Other Names: breath-actuated inhaler; Drug: Beclomethasone dipropionate MDI; 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.; Other Names: BDP; QVAR®; metered-dose inhaler
ACTIVE_COMPARATOR: BDP 160 mcg MDI; 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: albuterol/salbutamol 90 mcg; 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.; Other Names: bronchodilators; Drug: Placebo BAI; Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.; Other Names: breath-actuated inhaler; Drug: Beclomethasone dipropionate MDI; 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.; Other Names: BDP; QVAR®; metered-dose inhaler
PLACEBO_COMPARATOR: Placebo BAI and MDI; 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: albuterol/salbutamol 90 mcg; 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.; Other Names: bronchodilators; Drug: Placebo MDI; Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.; Drug: Placebo BAI; Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.; Other Names: breath-actuated inhaler

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Vandewalker M, Hickey L, Small CJ. Efficacy and safety of beclomethasone dipropionate breath-actuated or metered-dose inhaler in pediatric patients with asthma. Allergy Asthma Proc. 2017 Sep 14;38(5):354-364. doi: 10.2500/aap.2017.38.4078. Epub 2017 Jul 14.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: January 16, 2014
• First Submitted That Met QC Criteria: January 16, 2014
• First Posted (ESTIMATE): January 20, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: asthma; breath-actuated inhaler; metered dose inhaler
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Beclomethasone; Bronchodilator Agents
• Other Study ID Numbers: BDB-AS-302; 2013-004632-30 (EUDRACT_NUMBER)