Asthma
Conditions
Keywords
Fast-acting β2-agonist, Metered-Dose Inhaler (MDI), Bronchodilatory, Inhaled corticosteroids, Anti-inflammatory, Rescue Therapy
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed clinical diagnosis of asthma at least 12 months. * Receiving one of the following scheduled asthma maintenance therapies for at least 3 months with stable dosing for at least the last one month 1. Low-to-high-dose Inhaled corticosteroid(s) (ICS) 2. Low-to-high-dose ICS or ICS/long-acting β2-agonist (LABA) with or without one additional maintenance therapy from the following: leukotriene receptor antagonist (LTRA), long-acting muscarinic antagonist (LAMA), or theophylline * Receiving inhaled short-acting β2-agonist (SABA) as needed. * A documented history of at least one severe asthma exacerbation within 12 months. * Use of Sponsor-provided albuterol sulfate inhalation aerosol medication. * Demonstrate acceptable MDI administration technique as assessed by the investigator; use of spacers is prohibited. * Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator. * Participants must adhere to protocol specific contraception methods. * Negative urine pregnancy test for participants of childbearing potential. * Have a BMI \< 40 kg/ m\^2. * Capable of giving assent (signing the assent form) to participate in the study which includes compliance with the requirements and restrictions. The caregiver of the patient must be capable of giving written informed consent for the patient's participation in the study. Consent and assent forms must be completed prior to any study-specific procedures.
Exclusion criteria
* Life-threatening asthma defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s). * Experienced \> 3 severe asthma exacerbations within 12 months before screening. * Completed treatment for lower respiratory infection and severe asthma exacerbation with SCS within 4 weeks of screening. * Upper respiratory infection involving antibiotic treatment not resolved. * Current smokers, former smokers with \> 10 pack-years history, or former smokers who stopped smoking \< 6 months (including all forms of tobacco, e-cigarettes \[vaping\], and marijuana). * Other significant lung disease, including regular or occasional use of oxygen. * Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neuropsychological, endocrine, or gastrointestinal disorders. * Cancer not in complete remission for at least 5 years. * History or hospitalization for psychiatric disorder or attempted suicide within one year. * Significant abuse of alcohol or drugs, in the opinion of the investigator. * Oral corticosteroid(s) (OCS)/SCS use (any dose and any indication) within 4 weeks before Visit 1 or chronic use of OCS/SCS (≥ 3 weeks use in 3 months prior to Visit 1). * Use of any oral SABAs within one month. * Having a known or suspected hypersensitivity to albuterol/salbutamol, or budesonide and/or their excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of severe asthma exacerbations (AAER) | From Randomization (Day 1) to Week 52 (EOT) | The effect of BDA MDI compared with AS MDI, both administered as needed, on the AAER in participants with asthma will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first (TTF) severe asthma exacerbation | From Randomization (Day 1) to Week 52 (EOT) | 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. |
| Annualized total systemic corticosteroids (SCS) exposure for treatment of asthma | From Randomization (Day 1) to Week 52 (EOT) | 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. |
| Number of participants with adverse events (AEs) and severe adverse events (SAEs) | Up to Week 52 | The safety and tolerability of BDA MDI compared with AS MDI in participants with asthma will be assessed. |
| Maximum Observed Concentration (Cmax) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Area under concentration-time curve from time 0 to last quantifiable concentration (AUClast) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Area under concentration-time curve from time 0 to infinity (AUCinf) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Time to reach maximum concentration following drug administration (Tmax) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Time of last quantifiable concentration (Tlast) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Terminal elimination half-life (t½λz) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Terminal elimination rate constant (λz) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Apparent total body clearance (CL/F) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
| Apparent volume of distribution based on the terminal phase (Vz/F) | At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose | The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized. |
Countries
China, Mexico, South Africa, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed