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
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02040766
Collaborator
(none)
628
102
5
27
6.2
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
628 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Study Start Date
:
Dec 1, 2013
Actual Primary Completion Date
:
Feb 1, 2016
Actual Study Completion Date
:
Mar 1, 2016
Arms and Interventions
| 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:
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:
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:
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:
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: Placebo BAI
Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.
Other Names:
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:
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:
|
| 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: Placebo BAI
Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.
Other Names:
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:
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:
|
| 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: Placebo BAI
Placebo was delivered by a single inhalation using a breath-actuated inhaler (BAI) twice each day.
Other Names:
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:
Drug: Placebo MDI
Placebo was delivered by a single inhalation using a metered-dose inhaler (MDI) twice each day.
|
Outcome Measures
Primary Outcome Measures
- 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
- Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period [Day 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 Period [Day 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 Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1-12 [Day 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 the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12 [Day 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 Period [Day 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Years
to 11 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Teva Investigational Site 12346 | Hoover | Alabama | United States | |
| 2 | Teva Investigational Site 12294 | Montgomery | Alabama | United States | |
| 3 | Teva Investigational Site 10925 | Phoenix | Arizona | United States | |
| 4 | Teva Investigational Site 12349 | Little Rock | Arkansas | United States | |
| 5 | Teva Investigational Site 10903 | Costa Mesa | California | United States | |
| 6 | Teva Investigational Site 10911 | Downey | California | United States | |
| 7 | Teva Investigational Site 10901 | Huntington Beach | California | United States | |
| 8 | Teva Investigational Site 12297 | Huntington Beach | California | United States | |
| 9 | Teva Investigational Site 10880 | Mission Viejo | California | United States | |
| 10 | Teva Investigational Site 10895 | Orange | California | United States | |
| 11 | Teva Investigational Site 10924 | Paramount | California | United States | |
| 12 | Teva Investigational Site 10910 | Rolling Hills Estates | California | United States | |
| 13 | Teva Investigational Site 12343 | Roseville | California | United States | |
| 14 | Teva Investigational Site 12298 | San Diego | California | United States | |
| 15 | Teva Investigational Site 12300 | San Diego | California | United States | |
| 16 | Teva Investigational Site 12295 | San Jose | California | United States | |
| 17 | Teva Investigational Site 12312 | West Covina | California | United States | |
| 18 | Teva Investigational Site 10937 | Centennial | Colorado | United States | |
| 19 | Teva Investigational Site 10899 | Colorado Springs | Colorado | United States | |
| 20 | Teva Investigational Site 10894 | Aventura | Florida | United States | |
| 21 | Teva Investigational Site 12335 | Gainesville | Florida | United States | |
| 22 | Teva Investigational Site 12336 | Homestead | Florida | United States | |
| 23 | Teva Investigational Site 12345 | Homestead | Florida | United States | |
| 24 | Teva Investigational Site 12315 | Miami | Florida | United States | |
| 25 | Teva Investigational Site 12341 | Miami | Florida | United States | |
| 26 | Teva Investigational Site 12342 | Miami | Florida | United States | |
| 27 | Teva Investigational Site 10919 | Orlando | Florida | United States | |
| 28 | Teva Investigational Site 12281 | Sarasota | Florida | United States | |
| 29 | Teva Investigational Site 12332 | Winter Park | Florida | United States | |
| 30 | Teva Investigational Site 10935 | Gainesville | Georgia | United States | |
| 31 | Teva Investigational Site 10912 | Lawrenceville | Georgia | United States | |
| 32 | Teva Investigational Site 10927 | Savannah | Georgia | United States | |
| 33 | Teva Investigational Site 10885 | Owensboro | Kentucky | United States | |
| 34 | Teva Investigational Site 12317 | Covington | Louisiana | United States | |
| 35 | Teva Investigational Site 12296 | Baltimore | Maryland | United States | |
| 36 | Teva Investigational Site 12323 | White Marsh | Maryland | United States | |
| 37 | Teva Investigational Site 10897 | North Dartmouth | Massachusetts | United States | |
| 38 | Teva Investigational Site 10932 | Ypsilanti | Michigan | United States | |
| 39 | Teva Investigational Site 10914 | Plymouth | Minnesota | United States | |
| 40 | Teva Investigational Site 10917 | Columbia | Missouri | United States | |
| 41 | Teva Investigational Site 10916 | Rolla | Missouri | United States | |
| 42 | Teva Investigational Site 12331 | Missoula | Montana | United States | |
| 43 | Teva Investigational Site 10922 | Brick | New Jersey | United States | |
| 44 | Teva Investigational Site 10909 | Ocean City | New Jersey | United States | |
| 45 | Teva Investigational Site 12289 | Verona | New Jersey | United States | |
| 46 | Teva Investigational Site 10939 | Asheville | North Carolina | United States | |
| 47 | Teva Investigational Site 12348 | Charlotte | North Carolina | United States | |
| 48 | Teva Investigational Site 10893 | Raleigh | North Carolina | United States | |
| 49 | Teva Investigational Site 10888 | Canton | Ohio | United States | |
| 50 | Teva Investigational Site 12302 | Fairfield | Ohio | United States | |
| 51 | Teva Investigational Site 10921 | Toledo | Ohio | United States | |
| 52 | Teva Investigational Site 12285 | Toledo | Ohio | United States | |
| 53 | Teva Investigational Site 10906 | Oklahoma City | Oklahoma | United States | |
| 54 | Teva Investigational Site 10915 | Oklahoma City | Oklahoma | United States | |
| 55 | Teva Investigational Site 12314 | Oklahoma City | Oklahoma | United States | |
| 56 | Teva Investigational Site 10891 | Tulsa | Oklahoma | United States | |
| 57 | Teva Investigational Site 10892 | Medford | Oregon | United States | |
| 58 | Teva Investigational Site 10898 | Portland | Oregon | United States | |
| 59 | Teva Investigational Site 12273 | Pittsburgh | Pennsylvania | United States | |
| 60 | Teva Investigational Site 12282 | Warwick | Rhode Island | United States | |
| 61 | Teva Investigational Site 10902 | North Charleston | South Carolina | United States | |
| 62 | Teva Investigational Site 10938 | Orangeburg | South Carolina | United States | |
| 63 | Teva Investigational Site 12347 | Beaumont | Texas | United States | |
| 64 | Teva Investigational Site 10926 | Boerne | Texas | United States | |
| 65 | Teva Investigational Site 10908 | Dallas | Texas | United States | |
| 66 | Teva Investigational Site 10918 | Dallas | Texas | United States | |
| 67 | Teva Investigational Site 12291 | El Paso | Texas | United States | |
| 68 | Teva Investigational Site 12329 | Live Oak | Texas | United States | |
| 69 | Teva Investigational Site 10890 | New Braunfels | Texas | United States | |
| 70 | Teva Investigational Site 10904 | San Antonio | Texas | United States | |
| 71 | Teva Investigational Site 10929 | San Antonio | Texas | United States | |
| 72 | Teva Investigational Site 10879 | Waco | Texas | United States | |
| 73 | Teva Investigational Site 10883 | Richmond | Virginia | United States | |
| 74 | Teva Investigational Site 10886 | Bellingham | Washington | United States | |
| 75 | Teva Investigational Site 10913 | Greenfield | Wisconsin | United States | |
| 76 | Teva Investigational Site 60017 | Cakovec | Croatia | ||
| 77 | Teva Investigational Site 60018 | Zagreb | Croatia | ||
| 78 | Teva Investigational Site 60019 | Zagreb | Croatia | ||
| 79 | Teva Investigational Site 21037 | Guadalajara | Mexico | ||
| 80 | Teva Investigational Site 21042 | Guadalajara | Mexico | ||
| 81 | Teva Investigational Site 21039 | Mexico City | Mexico | ||
| 82 | Teva Investigational Site 21045 | Mexico City | Mexico | ||
| 83 | Teva Investigational Site 21035 | Monterrey | Mexico | ||
| 84 | Teva Investigational Site 21043 | San Lucas Tepetlacalco | Mexico | ||
| 85 | Teva Investigational Site 21047 | San Lucas Tepetlacalco | Mexico | ||
| 86 | Teva Investigational Site 21051 | Zapopan | Mexico | ||
| 87 | Teva Investigational Site 53276 | Bialystok | Poland | ||
| 88 | Teva Investigational Site 53267 | Krakow | Poland | ||
| 89 | Teva Investigational Site 53269 | Lodz | Poland | ||
| 90 | Teva Investigational Site 53272 | Lodz | Poland | ||
| 91 | Teva Investigational Site 53271 | Lublin | Poland | ||
| 92 | Teva Investigational Site 53274 | Lublin | Poland | ||
| 93 | Teva Investigational Site 53273 | Tarnow | Poland | ||
| 94 | Teva Investigational Site 53275 | Wroclaw | Poland | ||
| 95 | Teva Investigational Site 53270 | Zawadzkie | Poland | ||
| 96 | Teva Investigational Site 58165 | Dnipropetrovsk | Ukraine | ||
| 97 | Teva Investigational Site 58171 | Kharkiv | Ukraine | ||
| 98 | Teva Investigational Site 58168 | Kryvyi Rih | Ukraine | ||
| 99 | Teva Investigational Site 58167 | Kyiv | Ukraine | ||
| 100 | Teva Investigational Site 58172 | Kyiv | Ukraine | ||
| 101 | Teva Investigational Site 58169 | Zaporizhzhia | Ukraine | ||
| 102 | Teva Investigational Site 58170 | Zaporizhzhya | Ukraine |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02040766
Other Study ID Numbers:
- BDB-AS-302
- 2013-004632-30
First Posted:
Jan 20, 2014
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021
Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Patients were screened at 123 centers in Croatia, Mexico, Poland, Ukraine, and the United States. The intent-to-treat (ITT) population included all randomly assigned patients |
|---|---|
| Pre-assignment Detail | Patients were randomly assigned to treatment through a qualified randomization service provider. This system was used to ensure a balance across treatment groups, within each stratum |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | |||||
| STARTED | 127 | 126 | 125 | 125 | 125 |
| COMPLETED | 109 | 116 | 113 | 112 | 112 |
| NOT COMPLETED | 18 | 10 | 12 | 13 | 13 |
Baseline Characteristics
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 127 | 126 | 125 | 125 | 125 | 628 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
8.2
(2.06)
|
8.5
(2.10)
|
8.4
(1.24)
|
8.2
(1.78)
|
8.4
(1.86)
|
8.3
(1.93)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
41
32.3%
|
52
41.3%
|
46
36.8%
|
49
39.2%
|
50
40%
|
238
37.9%
|
| Male |
86
67.7%
|
74
58.7%
|
79
63.2%
|
76
60.8%
|
75
60%
|
390
62.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
3
2.4%
|
4
3.2%
|
4
3.2%
|
3
2.4%
|
1
0.8%
|
15
2.4%
|
| Asian |
0
0%
|
2
1.6%
|
2
1.6%
|
0
0%
|
0
0%
|
4
0.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
42
33.1%
|
34
27%
|
33
26.4%
|
37
29.6%
|
49
39.2%
|
195
31.1%
|
| White |
71
55.9%
|
69
54.8%
|
69
55.2%
|
76
60.8%
|
63
50.4%
|
348
55.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
11
8.7%
|
17
13.5%
|
17
13.6%
|
9
7.2%
|
12
9.6%
|
66
10.5%
|
Outcome Measures
| Title | 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)) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 (baseline), Weeks 2, 4, 8, 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all patients in the ITT population who received at least 1 dose of study drug and had at least 1 post baseline trough morning (pre-dose and pre-rescue bronchodilator) assessment of percent predicted FEV1. |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 113 | 111 | 116 | 114 | 114 |
| Least Squares Mean (Standard Error) [liters] |
2.62
(0.744)
|
5.43
(0.742)
|
3.25
(0.732)
|
3.54
(0.734)
|
3.71
(0.734)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ANCOVA model with effects due to baseline trough morning percent predicted FEV1, sex, age, current protocol-allowed asthma therapy (inhaled corticosteroid (ICS) or non-corticosteroid (NCS) therapy) at the time of screening visit, during the run-in period, and during treatment. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0063 |
| Comments | significance at 0.05. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.81 | |
| Confidence Interval |
(2-Sided) 95% 0.796 to 4.821 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ANCOVA model with effects due to baseline trough morning percent predicted FEV1, sex, age, current protocol-allowed asthma therapy (ICS or NCS therapy) at the time of screening visit, during the run-in period, and during treatment. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5332 |
| Comments | significance at 0.05. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.63 | |
| Confidence Interval |
(2-Sided) 95% -1.354 to 2.614 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ANCOVA model with effects due to baseline trough morning percent predicted FEV1, sex, age, current protocol-allowed asthma therapy (ICS or NCS therapy) at the time of screening visit, during the run-in period, and during treatment. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3649 |
| Comments | significance at 0.05 | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.92 | |
| Confidence Interval |
(2-Sided) 95% -1.077 to 2.924 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2823 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 95% -0.902 to 3.088 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Day 1 (baseline), weeks 1-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 124 | 124 | 122 | 121 | 123 |
| Least Squares Mean (Standard Error) [liters] |
4.3
(2.11)
|
15.6
(2.08)
|
12.8
(2.12)
|
11.9
(2.11)
|
10.8
(2.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.3 | |
| Confidence Interval |
(2-Sided) 95% 5.58 to 17.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0041 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.5 | |
| Confidence Interval |
(2-Sided) 95% 2.71 to 14.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0103 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.6 | |
| Confidence Interval |
(2-Sided) 95% 1.79 to 13.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0278 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 6.5 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 12.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Day 1 (baseline), weeks 1-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 124 | 124 | 122 | 121 | 123 |
| Least Squares Mean (Standard Error) [liters] |
1.4
(2.11)
|
13.1
(2.09)
|
11.4
(2.12)
|
11.3
(2.12)
|
10.1
(2.12)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.7 | |
| Confidence Interval |
(2-Sided) 95% 5.96 to 17.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 10.0 | |
| Confidence Interval |
(2-Sided) 95% 4.20 to 15.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.9 | |
| Confidence Interval |
(2-Sided) 95% 4.11 to 15.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0031 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.7 | |
| Confidence Interval |
(2-Sided) 95% 2.95 to 14.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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). |
| Time Frame | Day 1 (baseline), weeks 1-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 124 | 124 | 122 | 121 | 123 |
| Least Squares Mean (Standard Error) [Number of inhalations] |
-0.36
(0.069)
|
-0.72
(0.068)
|
-0.50
(0.069)
|
-0.41
(0.069)
|
-0.54
(0.069)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 95% -0.548 to -0.174 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1320 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -0.331 to 0.044 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5866 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.240 to 0.136 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0587 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.369 to 0.007 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1-12 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 (baseline), weeks 1-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 124 | 124 | 122 | 121 | 123 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.27
(0.036)
|
-0.44
(0.036)
|
-0.36
(0.036)
|
-0.31
(0.036)
|
-0.36
(0.036)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0011 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.261 to -0.065 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0869 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.185 to 0.013 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4388 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.138 to 0.060 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1041 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.180 to 0.017 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Kaplan-Meier Estimates For Time to Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 124 | 124 | 122 | 121 | 123 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
NA
|
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2870 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg BAI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5257 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 80 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9982 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo BAI and MDI, BDP 160 mcg MDI |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7633 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Adverse Events
| Time Frame | - Run-In: Days -21 to Day 0 - Double-blind Study Treatment: Day 1 to Week 12 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Run-In Placebo arm includes participants who were randomized. | |||||||||||
| Arm/Group Title | Run-in Placebo | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI | ||||||
| Arm/Group Description | Placebo was administered via breath-actuated inhaler (BAI) twice daily. Additionally placebo was administered via metered-dose inhaler (MDI) twice daily. Both were single-blind therapies giving participants experience with the devices. Prestudy asthma medications were adjusted according to the protocol. Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) at 90 mcg ex-actuator) or equivalent was used as rescue medication throughout the study. | 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. | 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. | 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. | 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. | 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. | ||||||
All Cause Mortality |
||||||||||||
| Run-in Placebo | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| Run-in Placebo | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/628 (0%) | 0/127 (0%) | 0/126 (0%) | 0/125 (0%) | 0/125 (0%) | 0/125 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| Run-in Placebo | Placebo BAI and MDI | BDP 80 mcg BAI | BDP 160 mcg BAI | BDP 80 mcg MDI | BDP 160 mcg MDI | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/628 (0.2%) | 8/127 (6.3%) | 6/126 (4.8%) | 13/125 (10.4%) | 15/125 (12%) | 11/125 (8.8%) | ||||||
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 0/628 (0%) | 0 | 4/127 (3.1%) | 5 | 5/126 (4%) | 6 | 11/125 (8.8%) | 14 | 6/125 (4.8%) | 7 | 6/125 (4.8%) | 7 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 1/628 (0.2%) | 1 | 4/127 (3.1%) | 7 | 1/126 (0.8%) | 1 | 3/125 (2.4%) | 3 | 9/125 (7.2%) | 11 | 6/125 (4.8%) | 7 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
| Name/Title | Director, Clinical Research |
|---|---|
| Organization | Teva Branded Pharmaceutical Products R&D, Inc. |
| Phone | 215-591-3000 |
| ustevatrials@tevapharm.com |
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02040766
Other Study ID Numbers:
- BDB-AS-302
- 2013-004632-30
First Posted:
Jan 20, 2014
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021