A Safety and Efficacy Study of Beclomethasone Dipropionat... | NCT02040766

NCT02040766

ID	Type	Description	Link
2013-004632-30	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BDP 80 mcg BAI	Experimental	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 Drug: albuterol/salbutamol 90 mcg Drug: Placebo MDI
BDP 160 mcg BAI	Experimental	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 Drug: albuterol/salbutamol 90 mcg Drug: Placebo MDI
BDP 80 mcg MDI	Active Comparator	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 Drug: albuterol/salbutamol 90 mcg Drug: Beclomethasone dipropionate MDI
BDP 160 mcg MDI	Active Comparator	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Beclomethasone dipropionate BAI	Drug	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.

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Over the 12-week Treatment Period	The analysis of change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF calculated across the 12-week treatment period was performed using a mixed model for repeated measures (MMRM) with effects due to baseline weekly average of daily trough morning PEF.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Teva Medical Expert, MD	Teva Branded Pharmaceutical Products R&D, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 12346		Hoover	Alabama		United States
Teva Investigational Site 12294

PubMed Identifier	Type	Citation	Retractions
28710850	Result	Vandewalker M, Hickey L, Small CJ. Efficacy and safety of beclomethasone dipropionate breath-actuated or metered-dose inhaler in pediatric patients with asthma. Allergy Asthma Proc. 2017 Sep 14;38(5):354-364. doi: 10.2500/aap.2017.38.4078. Epub 2017 Jul 14.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Least Squares Mean

Standard Error

liters

Day 1 (baseline), Weeks 2, 4, 8, 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.

Units	Counts
Participants	OG000113 OG001111 OG002116 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.62± 0.744 OG0015.43± 0.742 OG0023.25± 0.732 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	ANCOVA		0.0063	significance at 0.05.	Mean Difference (Final Values)	2.81			2-Sided	95	0.796	4.821					Superiority

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.

Full analysis set

Posted

Least Squares Mean

Standard Error

liters

Day 1 (baseline), weeks 1-12

ID	Title	Description
OG000	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.
OG001	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.
OG002	BDP 160 mcg BAI

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.

Full analysis set

Posted

Least Squares Mean

Standard Error

liters

Day 1 (baseline), weeks 1-12

ID	Title	Description
OG000	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.
OG001	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.
OG002	BDP 160 mcg BAI

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).

Full analysis set

Posted

Least Squares Mean

Standard Error

Number of inhalations

Day 1 (baseline), weeks 1-12

ID	Title	Description
OG000	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.
OG001	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.
OG002	BDP 160 mcg BAI

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.

Full analysis set

Posted

Least Squares Mean

Standard Error

units on a scale

Day 1 (baseline), weeks 1-12

ID	Title	Description
OG000	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.
OG001	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.

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.

Full analysis set

Posted

Median

95% Confidence Interval

Days

Day 1 to 12 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	BDP 160 mcg BAI

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Run-in Placebo	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.	628	1	628
EG001	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.	127	8	127
EG002	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.	126	6	126
EG003	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.	125	13	125
EG004	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.	125	15	125
EG005	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.	125	11	125

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA (16.1)	Systematic Assessment		EG0000 events0 affected628 at risk EG0015 events4 affected127 at risk EG0026 events5 affected126 at risk EG00314 events11 affected125 at risk EG0047 events6 affected125 at risk EG0057 events6 affected125 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment		EG0001 events1 affected628 at risk EG0017 events4 affected127 at risk EG0021 events1 affected126 at risk EG003

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D001507	Beclomethasone
D000420	Albuterol
D001993	Bronchodilator Agents
D036501	Metered Dose Inhalers

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013258	Steroids, Chlorinated
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines
D001337	Autonomic Agents
D018373	Peripheral Nervous System Agents
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D018927	Anti-Asthmatic Agents
D019141	Respiratory System Agents
D045506	Therapeutic Uses
D009330	Nebulizers and Vaporizers
D004864	Equipment and Supplies