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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

Phase 3
Completed
Conditions
Asthma
Interventions
Drug: Beclomethasone dipropionate BAI
Drug: Placebo BAI
Drug: albuterol/salbutamol 90 mcg
Drug: Placebo MDI
Drug: Beclomethasone dipropionate MDI
Registration Number
NCT02040766
Lead Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
628
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BDP 80 mcg BAIBeclomethasone dipropionate BAIBeclomethasone 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.
BDP 80 mcg BAIalbuterol/salbutamol 90 mcgBeclomethasone 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.
BDP 80 mcg BAIPlacebo MDIBeclomethasone 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.
BDP 160 mcg BAIBeclomethasone dipropionate BAIBeclomethasone 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.
BDP 160 mcg BAIalbuterol/salbutamol 90 mcgBeclomethasone 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.
BDP 160 mcg BAIPlacebo MDIBeclomethasone 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.
BDP 160 mcg MDIBeclomethasone dipropionate MDIBeclomethasone 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.
BDP 80 mcg MDIPlacebo BAIBeclomethasone 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.
BDP 80 mcg MDIalbuterol/salbutamol 90 mcgBeclomethasone 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.
BDP 80 mcg MDIBeclomethasone dipropionate MDIBeclomethasone 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.
BDP 160 mcg MDIPlacebo BAIBeclomethasone 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.
Placebo BAI and MDIPlacebo BAIPlacebo 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.
BDP 160 mcg MDIalbuterol/salbutamol 90 mcgBeclomethasone 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.
Placebo BAI and MDIalbuterol/salbutamol 90 mcgPlacebo 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.
Placebo BAI and MDIPlacebo MDIPlacebo 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.
Primary Outcome Measures
NameTimeMethod
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))Day 1 (baseline), Weeks 2, 4, 8, 12

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in the Weekly Average of Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1-12Day 1 (baseline), 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).

Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment PeriodDay 1 (baseline), weeks 1-12

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.

Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-week Treatment PeriodDay 1 (baseline), weeks 1-12

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.

Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12Day 1 (baseline), 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.

Kaplan-Meier Estimates For Time to Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-week Treatment PeriodDay 1 to 12 weeks

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.

Trial Locations

Locations (102)

Teva Investigational Site 10894

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Aventura, Florida, United States

Teva Investigational Site 12332

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Winter Park, Florida, United States

Teva Investigational Site 10916

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Rolla, Missouri, United States

Teva Investigational Site 12294

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Montgomery, Alabama, United States

Teva Investigational Site 53275

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Wroclaw, Poland

Teva Investigational Site 58167

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Kyiv, Ukraine

Teva Investigational Site 58172

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Kyiv, Ukraine

Teva Investigational Site 12315

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Miami, Florida, United States

Teva Investigational Site 12342

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Miami, Florida, United States

Teva Investigational Site 53272

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Lodz, Poland

Teva Investigational Site 53270

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Zawadzkie, Poland

Teva Investigational Site 12298

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San Diego, California, United States

Teva Investigational Site 12300

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San Diego, California, United States

Teva Investigational Site 58165

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Dnipropetrovsk, Ukraine

Teva Investigational Site 10925

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Phoenix, Arizona, United States

Teva Investigational Site 10906

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Oklahoma City, Oklahoma, United States

Teva Investigational Site 10915

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Oklahoma City, Oklahoma, United States

Teva Investigational Site 12314

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Oklahoma City, Oklahoma, United States

Teva Investigational Site 10898

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Portland, Oregon, United States

Teva Investigational Site 10904

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San Antonio, Texas, United States

Teva Investigational Site 10929

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San Antonio, Texas, United States

Teva Investigational Site 10917

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Columbia, Missouri, United States

Teva Investigational Site 10891

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Tulsa, Oklahoma, United States

Teva Investigational Site 10927

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Savannah, Georgia, United States

Teva Investigational Site 12346

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Hoover, Alabama, United States

Teva Investigational Site 10911

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Downey, California, United States

Teva Investigational Site 10880

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Mission Viejo, California, United States

Teva Investigational Site 12297

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Huntington Beach, California, United States

Teva Investigational Site 10903

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Costa Mesa, California, United States

Teva Investigational Site 10901

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Huntington Beach, California, United States

Teva Investigational Site 12349

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Little Rock, Arkansas, United States

Teva Investigational Site 10895

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Orange, California, United States

Teva Investigational Site 10924

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Paramount, California, United States

Teva Investigational Site 10910

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Rolling Hills Estates, California, United States

Teva Investigational Site 12343

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Roseville, California, United States

Teva Investigational Site 12295

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San Jose, California, United States

Teva Investigational Site 10937

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Centennial, Colorado, United States

Teva Investigational Site 12312

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West Covina, California, United States

Teva Investigational Site 10899

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Colorado Springs, Colorado, United States

Teva Investigational Site 12341

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Miami, Florida, United States

Teva Investigational Site 12345

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Homestead, Florida, United States

Teva Investigational Site 10912

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Lawrenceville, Georgia, United States

Teva Investigational Site 10935

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Gainesville, Georgia, United States

Teva Investigational Site 12281

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Sarasota, Florida, United States

Teva Investigational Site 12317

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Covington, Louisiana, United States

Teva Investigational Site 12296

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Baltimore, Maryland, United States

Teva Investigational Site 10885

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Owensboro, Kentucky, United States

Teva Investigational Site 10932

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Ypsilanti, Michigan, United States

Teva Investigational Site 10897

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North Dartmouth, Massachusetts, United States

Teva Investigational Site 12323

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White Marsh, Maryland, United States

Teva Investigational Site 10914

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Plymouth, Minnesota, United States

Teva Investigational Site 12336

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Homestead, Florida, United States

Teva Investigational Site 10922

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Brick, New Jersey, United States

Teva Investigational Site 10909

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Ocean City, New Jersey, United States

Teva Investigational Site 12289

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Verona, New Jersey, United States

Teva Investigational Site 10893

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Raleigh, North Carolina, United States

Teva Investigational Site 10939

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Asheville, North Carolina, United States

Teva Investigational Site 12348

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Charlotte, North Carolina, United States

Teva Investigational Site 10888

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Canton, Ohio, United States

Teva Investigational Site 10921

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Toledo, Ohio, United States

Teva Investigational Site 12285

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Toledo, Ohio, United States

Teva Investigational Site 12302

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Fairfield, Ohio, United States

Teva Investigational Site 10892

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Medford, Oregon, United States

Teva Investigational Site 12282

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Warwick, Rhode Island, United States

Teva Investigational Site 10902

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North Charleston, South Carolina, United States

Teva Investigational Site 10938

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Orangeburg, South Carolina, United States

Teva Investigational Site 10908

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Dallas, Texas, United States

Teva Investigational Site 12347

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Beaumont, Texas, United States

Teva Investigational Site 10926

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Boerne, Texas, United States

Teva Investigational Site 10918

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Dallas, Texas, United States

Teva Investigational Site 12329

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Live Oak, Texas, United States

Teva Investigational Site 12291

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El Paso, Texas, United States

Teva Investigational Site 10890

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New Braunfels, Texas, United States

Teva Investigational Site 10879

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Waco, Texas, United States

Teva Investigational Site 10886

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Bellingham, Washington, United States

Teva Investigational Site 10913

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Greenfield, Wisconsin, United States

Teva Investigational Site 60017

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Cakovec, Croatia

Teva Investigational Site 60019

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Zagreb, Croatia

Teva Investigational Site 60018

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Zagreb, Croatia

Teva Investigational Site 21042

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Guadalajara, Mexico

Teva Investigational Site 21039

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Mexico City, Mexico

Teva Investigational Site 21035

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Monterrey, Mexico

Teva Investigational Site 21047

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San Lucas Tepetlacalco, Mexico

Teva Investigational Site 21043

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San Lucas Tepetlacalco, Mexico

Teva Investigational Site 21051

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Zapopan, Mexico

Teva Investigational Site 53276

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Bialystok, Poland

Teva Investigational Site 53267

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Krakow, Poland

Teva Investigational Site 53274

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Lublin, Poland

Teva Investigational Site 58168

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Kryvyi Rih, Ukraine

Teva Investigational Site 53271

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Lublin, Poland

Teva Investigational Site 58171

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Kharkiv, Ukraine

Teva Investigational Site 58170

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Zaporizhzhya, Ukraine

Teva Investigational Site 58169

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Zaporizhzhia, Ukraine

Teva Investigational Site 12273

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Pittsburgh, Pennsylvania, United States

Teva Investigational Site 21037

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Guadalajara, Mexico

Teva Investigational Site 21045

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Mexico City, Mexico

Teva Investigational Site 12331

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Missoula, Montana, United States

Teva Investigational Site 53269

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Lodz, Poland

Teva Investigational Site 53273

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Tarnow, Poland

Teva Investigational Site 10919

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Orlando, Florida, United States

Teva Investigational Site 12335

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Gainesville, Florida, United States

Teva Investigational Site 10883

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Richmond, Virginia, United States

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