A 12-week Study to Assess the Efficacy and Safety of Bude... | NCT05755906

ID	Type	Description	Link
2021-003334-36	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
BFF MDI 160/9.6 μg BID (320/19.2μg/day)	Experimental	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), BDI (320/19.2μg/day)	Drug: BFF MDI 160/9.6 μg BID (320/19.2μg/day)
BD MDI 160 μg BID (320 μg/day)	Active Comparator	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)	Drug: BD MDI 160 μg BID (320 μg/day)

Name	Type	Description	Arm Group Labels	Other Names
BFF MDI 160/9.6 μg BID (320/19.2μg/day)	Drug	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)	BFF MDI 160/9.6 μg BID (320/19.2μg/day)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0 to 3 Hours (AUC0-3) at Week 12	Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 12. FEV1 AUC0-3 is calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time to report the result in liters. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.	At Week 12

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 12	Change from baseline in morning pre-dose trough FEV1 at Week 12. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

12 to 80 years of age, male and female, BMI <40 kg/m2; females of childbearing potential should be using highly effective birth control.
Participants who have a documented history of physician-diagnosed asthma ≥ 6 months prior to Visit 1, according to GINA guidelines [GINA 2021]. Healthcare records for one year prior to Visit 1 must be provided for adolescent participants (12 to < 18 years of age) to ensure consistent evaluation and follow-up of treatment in those participants.
Participants who have been regularly using a stable daily ICS or an ICS/LABA regimen (including a stable ICS dose), with allowed ICS doses, for at least 8 weeks prior to Visit 1.
ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
A pre-bronchodilator/pre-dose FEV1 < 90% predicted normal value at Visits 1, 2, and 3 and a pre-dose FEV1 of 50% to 90% at Visit 4 (pre-randomization).
Reversibility to albuterol, defined as a post-albuterol increase in FEV1 of ≥ 12% and ≥ 200 mL for participants ≥ 18 years of age OR a post-albuterol increase in FEV1 of ≥ 12% for participants 12 to < 18 years of age either in the 12 months prior to Visit 1 or at Visit 2 or Visit 3, if repeat testing is necessary.
A pre-bronchodilator/pre-dose FEV1 at Visits 2, 3, and 4 that has not changed 20% or more (increase or decrease) from the pre-bronchodilator/pre-dose FEV1 recorded at the previous visit.
Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment defined in Section 8.1.2.8 as a guideline.
Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
Demonstrate acceptable MDI administration technique.
eDiary compliance ≥ 70% during screening, defined as completing the daily eDiary and answering "Yes" to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization.

Exclusion criteria

Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).
Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the Screening Period.
Hospitalization for asthma within 8 weeks of Visit 1.
Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (eg, active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, and COPD). Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety analysis.
Known history of drug or alcohol abuse within 12 months of Visit 1.
Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin are not exclusionary.
Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration.
Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
Use of a nebulizer or a home nebulizer for receiving asthma medications. Note: Acute use of a nebulizer for an asthma exacerbation during hospitalization is allowed as long as there is no occurrence within 8 weeks of Visit 1.
Do not meet the stable dosing period prior to Visit 1 or unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.
Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg, vector, lipid nanoparticle) ≤7 days prior to Visit 1 (from last vaccination or booster dose).
Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study.
Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
Planned hospitalization during the study.
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements.
For women only - currently pregnant (confirmed with positive highly sensitive urine pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Chandler	Arizona	85224	United States
Research Site

Label	URL
CSR Synopsis	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
FG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 15, 2024	Oct 2, 2025

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00048.8± 16.6 BG00148.0± 16.1 BG00248.4± 16.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000113 BG001128 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Black or African American	BG00015 BG00119 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Global

Title	Measurements
Canada	BG00019 BG00113 BG002

Prior asthma medication

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
ICS	BG00043 BG00142 BG002

Baseline reversibility (%)

Reversibility (%) is calculated as (Post-Albuterol FEV1 - Pre-Albuterol FEV1)/Pre-Albuterol FEV1 x100

Mean

Standard Deviation

Percentage

Title

Denominators

Categories

Title	Measurements
	BG00021.8± 14.5 BG00121.0± 14.6

Baseline pre-bronchodilator FEV1 (L)

Baseline pre-bronchodilator FEV1 (L) is the mean of the pre-dose FEV1 at -60 and -30 minutes on Day 1, using the best effort at each timepoint.

Mean

Standard Deviation

Liter

Title

Denominators

Categories

Title	Measurements
	BG0002.097± 0.630 BG001

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

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0 to 3 Hours (AUC0-3) at Week 12

Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 12. FEV1 AUC0-3 is calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time to report the result in liters. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

The Efficacy Set is defined as all participants who are randomized to study intervention and receive any amount of randomized study intervention. Participants are analyzed according to the treatment assigned at randomization, regardless of the actual treatment received. Only subjects with non-missing baseline covariates used in the analysis model are included in the analysis.

Posted

Least Squares Mean

Standard Error

Liter

At Week 12

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Units	Counts
Participants	OG000175 OG001168

Title

Denominators

Categories

Title	Measurements
	OG0000.309± 0.0235 OG0010.109± 0.0241

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		<0.0001		Mean Difference (Final Values)	0.200	Standard Error of the Mean	0.0337	2-Sided	95	0.134	0.267			An increase in estimate favors study drug. The model includes treatment, visit, prior maintenance medication, treatment-by-visit interaction, baseline trough FEV1, and percent Albuterol reversibility.		Superiority

Secondary

Change From Baseline in Morning Pre-dose Trough FEV1 at Week 12

Change from baseline in morning pre-dose trough FEV1 at Week 12. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Least Squares Mean

Standard Error

Liter

At Week 12

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Units	Counts

Secondary

Onset of Action on Day 1: Absolute Change in FEV1 at 5 Minutes on Day 1

Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Least Squares Mean

Standard Error

Liter

On Day 1

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Units	Counts

Secondary

Change From Baseline in the Mean Number of Puffs of Rescue Medication Use (Puffs/Day) Over 12 Weeks

Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 12 Weeks. Baseline is the average during the last 7 days before randomization. Over 12 weeks is the average from randomization up to week 12. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Least Squares Mean

Standard Error

Puffs/Day

Over 12 Weeks

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Secondary

Percentage of Responders in ACQ-7 (≥ 0.5 Decrease Equals Response) at Week 12

Percentage of responders in ACQ-7 at Week 12, where responders are defined as participants with a ≥0.5 decrease in total score from baseline. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Number

Percentage of participants

At Week 12

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Secondary

Percentage of Responders in ACQ-5 (≥ 0.5 Decrease Equals Response) at Week 12

Percentage of responders in ACQ-5 at Week 12, where responders are defined as participants with a ≥0.5 decrease in total score from baseline. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Number

Percentage of participants

At Week 12

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Secondary

Percentage of Responders in the Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(s) +12) (≥ 0.5 Increase Equals Response) at Week 12

Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) at Week 12, where responders are defined as participants with a ≥0.5 increase in total score from baseline. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Number

Percentage of participants

At Week 12

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)

Secondary

Rate of Severe Asthma Exacerbation (Pooled LITHOS and VATHOS Data) During the Treatment Period (up to 24 Weeks)

As requested by a Health Authority, data from LITHOS and VATHOS (NCT05202262), two studies originally designed to assess lung function, were pooled to analyze the annualized rate of severe asthma exacerbations. This analysis was prespecified, uses data up to 12 weeks for LITHOS and 24 weeks for VATHOS, and was incorporated into the multiple testing procedure. An exacerbation is considered severe if it results in at least one of the following: a course of systemic corticosteroids (SCS) for ≥3 consecutive days to treat symptoms of asthma worsening, an ER or urgent care visit due to asthma requiring treatment with SCS, an in-patient hospitalization due to asthma, or death related to asthma. Treatment policy is implemented to handle all intercurrent events except for initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is used.

The Efficacy Set is defined as all participants in LITHOS and VATHOS (NCT05202262) who are randomized to study intervention and receive any amount of randomized study intervention. Participants are analyzed according to the treatment assigned at randomization, regardless of the actual treatment received. Only subjects with non-missing baseline covariates used in the analysis model are included in the analysis.

Posted

Least Squares Mean

Standard Error

Exacerbations/year

24 Weeks

ID	Title	Description
OG000	BFF MDI 160/9.6 μg or 320/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day) or Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 μg BID (640/19.2μg/day)

Secondary

Rate of Severe Asthma Exacerbation During the Treatment Period (up to 12 Weeks)

Annualized rate of severe asthma exacerbation during the treatment period (up to 12 Weeks). An asthma exacerbation will be considered severe if it results in at least one of the following: a course of systemic corticosteroids for at least 3 consecutive days to treat symptoms of asthma worsening, an ER or urgent care visit due to asthma that required treatment with systemic corticosteroids, an in-patient hospitalization due to asthma, or death related to asthma. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

Posted

Least Squares Mean

Standard Error

Exacerbations/year

12 Weeks

ID	Title	Description
OG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
OG001	BD MDI 160 μg

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)	0	179	0	179	9	179
EG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)	0	174	0	174	9	174

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment		EG0004 events3 affected179 at risk EG0014 events4 affected174 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 27.1	Systematic Assessment		EG0006 events6 affected179 at risk EG0017 events5 affected174 at risk

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	Title	Description
BG000	BFF MDI 160/9.6 μg	Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg BID (320/19.2μg/day)
BG001	BD MDI 160 μg	Budesonide (BD) metered-dose inhaler (MDI), 160 μg BID (320 μg/day)
BG002	Total	Total of all reporting groups