This is a 24 week study to evaluate the efficacy and safety of budesonide and formoterol fumarate metered dose inhaler in adults and adolescents with inadequately controlled asthma.
This is a Phase III randomized, double-blind, active comparison, parallel group, multicenter study comparing BFF MDI 320/9.6 μg to BD MDI 320 µg and open-label Symbicort TBH 320/9 μg in adult and adolescent participants who have asthma which remains inadequately controlled (ACQ-7 total score ≥ 1.5) despite treatment with medium dose ICS or ICS/LABA. Budesonide and Formoterol Fumarate MDI 160/9.6 μg is included in this study to evaluate dose response by comparing to BFF MDI 320/9.6 μg. All doses represent the sum of 2 actuations. All study interventions will be administered BID for 24 weeks. This study will be conducted at approximately 125 sites worldwide and will randomize approximately 630 adult and adolescent participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
645
Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 μg
Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg
Budesonide MDI (BD MDI), 320 μg
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0 to 3 Hours (AUC0-3) at Week 24
Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24. 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.
Time frame: At Week 24
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24
Change from baseline in morning pre-dose trough FEV1 at Week 24. 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.
Time frame: At 24 Weeks
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.
Time frame: On Day 1
Change From Baseline in the Mean Number of Puffs of Rescue Medication Use (Puffs/Day) Over 24 Weeks
Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks. Baseline is the average during the last 7 days before randomization. Over 24 weeks is the average from randomization up to week 24. 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.
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Open-label Symbicort Turbuhaler 320/9 μg
Research Site
Chandler, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Bakersfield, California, United States
Research Site
Fresno, California, United States
Research Site
Huntington Beach, California, United States
Research Site
La Palma, California, United States
Research Site
Lincoln, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
...and 132 more locations
Time frame: Over 24 Weeks
Percentage of Responders in ACQ-7 (≥ 0.5 Decrease Equals Response) at Week 24
Percentage of responders in ACQ-7 at Week 24, 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.
Time frame: At Week 24
Percentage of Responders in ACQ-5 (≥ 0.5 Decrease Equals Response) at Week 24
Percentage of responders in ACQ-5 at Week 24, 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.
Time frame: At Week 24
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 24
Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) at Week 24, 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.
Time frame: At Week 24
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 VATHOS and LITHOS (NCT05755906), 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.
Time frame: 24 Weeks
Rate of Severe Asthma Exacerbation During the Treatment Period (up to 24 Weeks)
Annualized rate of severe asthma exacerbation during the treatment period (up to 24 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.
Time frame: 24 Weeks