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

• ClinicalTrials.gov Identifier: NCT06307665
• Recruitment Status: Not yet recruiting
• First Posted: March 13, 2024
• Last Update Posted: April 9, 2024
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Combination Product: BDA MDI; Combination Product: AS MDI	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: May 8, 2024
• Estimated Primary Completion Date: October 13, 2027
• Estimated Study Completion Date: October 13, 2027

Arms and Interventions

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 Name: 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 Name: PT007

Outcome Measures

Primary Outcome Measures :

1. Annualized rate of severe asthma exacerbations (AAER) [ Time Frame: 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 Outcome Measures :

1. Time to first (TTF) severe asthma exacerbation [ Time Frame: 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.
2. Annualized total systemic corticosteroids (SCS) exposure for treatment of asthma [ Time Frame: 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.
3. Number of participants with adverse events (AEs) and severe adverse events (SAEs) [ Time Frame: Up to Week 52 ]
   The safety and tolerability of BDA MDI compared with AS MDI in participants with asthma will be assessed.
4. Maximum Observed Concentration (Cmax) [ Time Frame: 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.
5. Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) [ Time Frame: 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.
6. Area under plasma concentration-time curve from time 0 to infinity (AUCinf) [ Time Frame: 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.
7. Time to reach maximum concentration following drug administration (Tmax) [ Time Frame: 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.
8. Time to reach maximum concentration following drug administration (Tlast) [ Time Frame: 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.
9. Terminal elimination half-life (t½λz) [ Time Frame: 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.
10. Terminal elimination rate constant (λz) [ Time Frame: 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.
11. Apparent total body clearance (CL/F) [ Time Frame: 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.
12. Apparent volume of distribution based on the terminal phase (Vz/F) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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.

Contacts and Locations

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

Locations

United States, Maryland

Research Site

White Marsh, Maryland, United States, 21162

Sponsors and Collaborators

AstraZeneca

Parexel

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT06307665
• Other Study ID Numbers: D6934C00001
• First Posted: March 13, 2024
• Last Update Posted: April 9, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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.
• 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.
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by AstraZeneca:

Fast-acting β2-agonist; Metered-Dose Inhaler (MDI); Bronchodilatory; Inhaled corticosteroids; Anti-inflammatory; Rescue Therapy

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases