A Study to Assess the Efficacy and Safety of Budesonide/Albuterol Metered-dose Inhaler (BDA MDI/PT027) in Adults and Children 4 Years of Age or Older With Asthma

Study Overview
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Brief Summary
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This is a randomized, double-blind, multicenter, parallel-group, variable-length study to compare 2 doses of BDA MDI (PT027) with AS MDI (PT007) on the time to first severe asthma exacerbation in adult, adolescent, and pediatric subjects with moderate to severe asthma.

Official Title
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A Long-term, Randomized, Double-blind, Multicenter, Parallel-group, Phase III Study Evaluating the Efficacy and Safety of PT027 Compared to PT007 Administered as Needed in Response to Symptoms in Symptomatic Adults and Children 4 Years of Age or Older With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
* Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg
* Drug: Albuterol sulfate metered-dose inhaler 180 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male aged ≥4 years at the time of informed consent Physician diagnosis of asthma documented for at least 1 year Receiving 1 of the following scheduled asthma maintenance therapies for 3 months with stable dosing for at least the last 4 weeks before Visit 1: Medium-to-high-dose inhaled corticosteroid (ICS) Medium-to-high-dose ICS and 1 additional maintenance therapy from the following: leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA), or theophylline Low-to-high-dose ICS in combination with long-acting β2-adrenoreceptor agonist (LABA) with or without one additional maintenance therapy from the following: LTRA, LAMA, or theophylline Prebronchodilator forced expiratory volume in 1 second (FEV1) of ≥40 to <90% predicted normal value for adults and adolescents, and ≥60 to <100% predicted normal value for subjects aged 4 to 11 years after withholding specified medications including short/rapid-acting β2-adrenoreceptor agonist (SABA) Demonstrate reversibility at Visit 1, with an increase in FEV1 ≥12% (and ≥200 mL for subjects aged ≥18 years) relative to baseline after administration of sponsor provided Ventolin via central spirometry. One re-test for reversibility testing is allowed within the screening period in advance of Visit 2 Demonstrate acceptable spirometry performance (i.e., meet American Thoracic Society/European Respiratory Society acceptability/repeatability criteria) A documented history of at least 1 severe asthma exacerbation within 12 months before Visit 1 Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator Exclusion Criteria: Chronic obstructive pulmonary disease or other significant lung disease (e.g., chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia) Oral corticosteroid/SCS use (any dose and any indication) within 6 weeks before Visit 1 Chronic use of oral corticosteroids (OCS, ≥3 weeks use in 3 months prior to Visit 1) Having received any marketed (e.g., omalizumab, mepolizumab, reslizumab, benralizumab) or investigational biologic within 3 months or any other prohibited medication Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and marijuana) 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) within 5 years of Visit 1 Historical or current evidence of a clinically significant disease Cancer not in complete remission for at least 5 years Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1 History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity Significant abuse of alcohol or drugs

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BDA MDI (PT027) 160/180 μg<br>Budesonide/albuterol sulfate, BDA MDI, PT027 high dose | Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg<br>* Budesonide/albuterol sulfate combination inhalation aerosol<br>|
| Experimental: BDA MDI (PT027) 80/180 μg<br>Budesonide/albuterol sulfate, BDA MDI, PT027 low dose | Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg<br>* Budesonide/albuterol sulfate combination inhalation aerosol<br>|
| Active Comparator: AS MDI (PT007) 180 µg<br>Albuterol sulfate MDI, PT007 | Drug: Albuterol sulfate metered-dose inhaler 180 μg<br>* Albuterol sulfate inhalation aerosol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Severe Asthma Exacerbation Event | Time to first severe asthma exacerbation will be calculated as the time from randomization until the start date of the first severe asthma exacerbation. An asthma exacerbation will be considered severe if it results in at least one of the following: a temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days to treat symptoms of asthma worsening (a single depo-injectable dose of corticosteroids will be considered equivalent), an emergency room or urgent care visit (<24 hours in the facility for evaluation and treatment) due to asthma that required systemic corticosteroids, or an in-patient hospitalization (admission to an in-patient facility and/or ≥ 24 hours in a healthcare facility) due to asthma. The descriptive summary shows the number of participants with a severe exacerbation event, occurring between the date of randomization up to the date of randomized treatment discontinuation or a change in maintenance therapy. | From randomization up to a discontinuation of randomized treatment or a change in maintenance therapy. The mean and median reporting period for all participants was 44 and 48 weeks, respectively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Severe Exacerbation Rate | The annualized severe exacerbation rate (severe exacerbations per year) is estimated from a negative binomial model with treatment, age group, region, and number of severe exacerbations in the last 12 months prior to randomization as categorical covariates. The logarithm of the time at risk is included as an offset variable. | From randomization up to discontinuation of randomized treatment or a change in maintenance therapy. The mean and median reporting period for all participants was 44 and 48 weeks, respectively. | 
| Total Annualized Dose of Systemic Corticosteroid (SCS) | This endpoint includes all systemic corticosteroids (SCS) taken in response to a severe exacerbation event from randomization up to randomized treatment discontinuation or a change in maintenance therapy. All SCS are standardized to equipotent doses of prednisone before deriving the total dose. The total annualized dose is calculated as the total dose of SCS divided by the duration of the randomized treatment period. | From randomization up to discontinuation of randomized treatment or a change in maintenance therapy. The mean and median reporting period for all participants was 44 and 48 weeks, respectively. | 
| Asthma Control Questionnaire-5 (ACQ-5) - Number of Participants Who Were Responders at Week 24 | The ACQ-5 consists of 5 questions on symptom control, with each scored on a 7-point scale (0 = excellent asthma control; 6 = extremely poor control). The overall score (0 = excellent asthma control; 6 = extremely poor control, so a lower score is the better outcome) is the mean of the 5 symptom items. A responder is defined as a participant with a decrease from baseline to Week 24 overall ACQ-5 score of 0.5 or more. ACQ-5 is not validated for children less than 6 years old, data for participants who were 4 or 5 years old was excluded from the analysis of ACQ-5. | From baseline to Week 24 | 
| Asthma Quality of Life Questionnaire for Participants Aged 12 Years and Older (AQLQ+12) - Number of Participants Who Were Responders at Week 24 | The AQLQ+12 consists of 32 questions in 4 domains and is assessed on separate 7-point Likert scales from 1 to 7, with higher values indicating better health-related quality of life. The overall score is the mean of all responses. A responder is defined as a participant with an increase from baseline to week 24 AQLQ-12 score of at least 0.5. | From baseline to 24 weeks |