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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02040766
• Other study ID #: BDB-AS-302
• Secondary ID: 2013-004632-30
• Status: Completed
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: March 2016

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 628
• Est. completion date: March 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

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.
• Placebo BAI
Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.
• 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.
• 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.
• Placebo MDI
Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Croatia,  Mexico,  Poland,  Ukraine, 

References & Publications (1)

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 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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