The purpose of this study is to compare the effect of budesonide/albuterol metered-dose inhaler (BDA MDI) with albuterol sulfate metered-dose inhaler (AS MDI), both administered as needed, on the annualized rate of severe asthma exacerbations in adolescents with a documented clinical diagnosis of asthma and at least one severe exacerbation in the prior year.
This is a randomized, double-blind, multicenter, parallel-group Phase IIIb study with a fixed treatment period of 52 weeks. The study will consist of 3 periods: 1. Screening period (7 to 28 days) 2. Treatment period of 52 weeks 3. Safety follow-up period (7 to 14 days after the end of treatment \[EOT\] visit) Participants who meet the eligibility criteria will be randomly assigned to BDA MDI 160/180 micrograms (μg) or AS MDI 180 μg treatment groups in a 1:1 ratio on top of their own usual maintenance therapy during treatment period. This study will also include a pharmacokinetic (PK) sub-study with single visit scheduled after the safety follow-up visit in the main study. During PK sub-study, single dose of open-label BDA MDI 160/180 μg will be administered.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
440
Annualized rate of severe asthma exacerbations (AAER)
The effect of BDA MDI compared with AS MDI, both administered as needed, on the AAER in participants with asthma will be evaluated.
Time frame: From Randomization (Day 1) to Week 52 (EOT)
Time to first (TTF) severe asthma exacerbation
The effect of BDA MDI compared with AS MDI, both administered as needed, on the risk of a first severe asthma exacerbation in participants with asthma will be evaluated.
Time frame: From Randomization (Day 1) to Week 52 (EOT)
Annualized total systemic corticosteroids (SCS) exposure for treatment of asthma
The effect of BDA MDI compared with AS MDI, both administered as needed, on the annualized total SCS exposure for treatment of asthma in participants with asthma will be evaluated.
Time frame: From Randomization (Day 1) to Week 52 (EOT)
Number of participants with adverse events (AEs) and severe adverse events (SAEs)
The safety and tolerability of BDA MDI compared with AS MDI in participants with asthma will be assessed.
Time frame: Up to Week 52
Maximum Observed Concentration (Cmax)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Area under concentration-time curve from time 0 to last quantifiable concentration (AUClast)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
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Area under concentration-time curve from time 0 to infinity (AUCinf)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Time to reach maximum concentration following drug administration (Tmax)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Time of last quantifiable concentration (Tlast)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Terminal elimination half-life (t½λz)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Terminal elimination rate constant (λz)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Apparent total body clearance (CL/F)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Apparent volume of distribution based on the terminal phase (Vz/F)
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Time frame: At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose