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

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)

The purpose of this study is to compare the budesonide/albuterol metered-dose inhaler (BDA MDI) with albuterol sulfate metered-dose inhaler (AS MDI) administered as needed on severe asthma exacerbations in adolescent participants aged 12 to < 18 years with a documented clinical diagnosis of asthma and at least one severe exacerbation in the prior year.

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma
• Intervention / Treatment: Combination product: BDA MDI; Combination product: AS MDI

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.

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 β2-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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Budesonide/albuterol metered -dose inhaler (BDA MDI); Participants will receive BDA MDI 160/180 μg (given as 2 puffs of 80/90 μg) as needed.	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.; Other Names: PT027
Active Comparator: Albuterol sulfate metered-dose inhaler (AS MDI); Participants will receive AS MDI 180 μg (given as 2 puffs of 90 μg) as needed.	Combination product: AS MDI; Participants will receive oral inhalation of AS MDI 180 μg taken as 2 puffs of 90 μg as needed.; Other Names: PT007

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
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
Area under plasma 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
Area under plasma 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
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
Time to reach maximum concentration following drug administration (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
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.	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.	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.	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.	At 0, 10, 20, 40 minutes and 1, 2, 4, 6, 8, 10, and 12 hours post-dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2024
• Primary Completion (Estimated): October 13, 2027
• Study Completion (Estimated): October 13, 2027

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Anti-inflammatory; Inhaled corticosteroids; Rescue Therapy; Fast-acting β2-agonist; Metered-Dose Inhaler (MDI); Bronchodilatory
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D6934C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes