Evaluating the Efficacy and Safety of PT027 Compared With PT007 Administered As Needed in Participants 12 to < 18 Years of Age With Asthma

Asthma Clinical Trial

— ACADIA  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06307665
• Other study ID #: D6934C00001
• Status: Recruiting
• Phase: Phase 3
• Start date: May 20, 2024
• Est. completion date: October 6, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: October 6, 2027
• Est. primary completion date: October 6, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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 with or without long-acting ß2-agonist (LABA) and one additional maintenance therapy from the following: leukotriene receptor antagonist (LTRA), long-acting muscarinic antagonist (LAMA), or theophylline

• Receiving inhaled short-acting ß2-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.

Related Conditions & MeSH terms

• Asthma

Intervention

Combination Product:
• BDA MDI
Participants will receive oral inhalation of BDA MDI 160/180 µg taken as 2 puffs of 80/90 µg as needed.
• AS MDI
Participants will receive oral inhalation of AS MDI 180 µg taken as 2 puffs of 90 µg as needed.

Locations

Country	Name	City	State
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Austin	Texas
United States	Research Site	Beaumont	Texas
United States	Research Site	Bellingham	Washington
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Corsicana	Texas
United States	Research Site	Cortland	New York
United States	Research Site	Dallas	Texas
United States	Research Site	Destin	Florida
United States	Research Site	Detroit	Michigan
United States	Research Site	Hawthorne	New York
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Lafayette	Louisiana
United States	Research Site	Mankato	Minnesota
United States	Research Site	New York	New York
United States	Research Site	Newark	New Jersey
United States	Research Site	Ocean City	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	San Antonio	Texas
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Vestal	New York
United States	Research Site	Watertown	New York
United States	Research Site	White Marsh	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Randomization (Day 1) to Week 52 (EOT)
Secondary	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.	From Randomization (Day 1) to Week 52 (EOT)
Secondary	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.	From Randomization (Day 1) to Week 52 (EOT)
Secondary	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.	Up to Week 52
Secondary	Maximum Observed Concentration (Cmax)	The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	Terminal elimination half-life (t½?z)	The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	Terminal elimination rate constant (?z)	The PK of budesonide and albuterol in participants with asthma, following a single dose of BDA MDI will be characterized.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose
Secondary	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose