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.
Brief Title
Evaluating the Efficacy and Safety of PT027 Compared With PT007 Administered As Needed in Participants 12 to < 18 Years of Age With Asthma
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-877-240-9479
Central Contact Email
information.center@astrazeneca.com
Completion Date
Completion Date Type
Estimated
Conditions
Asthma
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Fast-acting β2-agonist
Metered-Dose Inhaler (MDI)
Bronchodilatory
Inhaled corticosteroids
Anti-inflammatory
Rescue Therapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
12 Years
NCT Id
NCT06307665
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D6934C00001
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized, Double-blind, Multicenter, Parallel-group, Phase IIIb 52 Week Study Evaluating the Efficacy and Safety of PT027 Compared With PT007 Administered as Needed in Participants 12 to < 18 Years of Age With Asthma (ACADIA)
Primary Outcomes
Outcome Description
The effect of BDA MDI compared with AS MDI, both administered as needed, on the AAER in participants with asthma will be evaluated.
Outcome Measure
Annualized rate of severe asthma exacerbations (AAER)
Outcome Time Frame
From Randomization (Day 1) to Week 52 (EOT)
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From Randomization (Day 1) to Week 52 (EOT)
Outcome Measure
Time to first (TTF) severe asthma exacerbation
Outcome Description
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.
Outcome Time Frame
From Randomization (Day 1) to Week 52 (EOT)
Outcome Measure
Annualized total systemic corticosteroids (SCS) exposure for treatment of asthma
Outcome Description
The safety and tolerability of BDA MDI compared with AS MDI in participants with asthma will be assessed.
Outcome Time Frame
Up to Week 52
Outcome Measure
Number of participants with adverse events (AEs) and severe adverse events (SAEs)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Maximum Observed Concentration (Cmax)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Area under concentration-time curve from time 0 to last quantifiable concentration (AUClast)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Area under concentration-time curve from time 0 to infinity (AUCinf)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Time to reach maximum concentration following drug administration (Tmax)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Time of last quantifiable concentration (Tlast)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Terminal elimination half-life (t½λz)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Terminal elimination rate constant (λz)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Apparent total body clearance (CL/F)
Outcome Description
The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.
Outcome Time Frame
At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Outcome Measure
Apparent volume of distribution based on the terminal phase (Vz/F)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jenny Shliozberg
Investigator Email
jshliozb@montefiore.org
Investigator Phone
jshliozb