A Study to Assess the Efficacy and Safety of Budesonide/Albuterol Metered Dose Inhaler (BDA MDI/PT027) Used 4 Times Daily in Adults and Children 4 Years of Age or Older With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose); Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose); Budesonide metered dose inhaler / BD MDI 160 µg; Albuterol sulfate metered dose inhaler / AS MDI 180 μg; Placebo metered-dose inhaler / Placebo MDI
Intervention description: Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 160/180 micrograms (μg), given as 2 inhalations of BDA MDI 80/90 μg, four times a day (QID); Budesonide/albuterol sulfate pressurized metered dose inhaler (BDA MDI) 80/180 micrograms (μg), given as 2 inhalations of BDA MDI 40/90 μg, four times a day (QID); Budesonide pressurized metered dose inhaler (BD MDI) 160 micrograms (μg), given as 2 inhalations of BD MDI 80 μg, four times a day (QID); Albuterol sulfate pressurized metered dose inhaler (AS MDI) 180 micrograms (μg), given as 2 inhalations of AS MDI 90 μg, four times a day (QID); Placebo pressurized metered dose inhaler (Placebo MDI), given as 2 inhalations of Placebo MDI, four times a day (QID)
Intervention MeSH terms: Budesonide; Albuterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1001.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No

Summary:

      This is a randomized, double-blind, placebo-controlled, multicenter, parallel group study to
      compare 2 dose levels of budesonide/albuterol BDA MDI (PT027) to its components budesonide BD
      MDI (PT008) and albuterol AS MDI (PT007) on improvement in lung function and asthma symptoms
      after 12 weeks of treatment in adult, adolescent, and child subjects with symptomatic asthma
      currently being treated with a short/rapid-acting β2-adrenoreceptor agonist (SABA) as needed
      alone or with low-dose inhaled corticosteroid (ICS) maintenance therapy plus SABA as needed.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female or male aged ≥4 years at the time of informed consent

          2. Physician diagnosis of asthma with a documented history of the last 6 months

          3. Receiving 1 of the following inhaled asthma medications with stable dosing for at
             least 30 days prior to Visit 1:

               -  Only short/rapid-acting β2-adrenoreceptor agonist (SABA) used as needed

               -  Stable low-dose inhaled corticosteroid in addition to as-needed use of SABA

          4. Pre-bronchodilator FEV1 of ≥50 to <85% predicted normal value for adults (≥18 years of
             age) and ≥50% predicted normal value for subjects aged 4 to 17 years after withholding
             SABA ≥6 hours at Visit 1.

          5. Demonstrate reversibility of airflow limitation defined as a ≥15% increase in FEV1
             relative to baseline after administration of Sponsor-provided SABA (Ventolin) at
             either Visit 1 or Visit 1a.

          6. Demonstrate acceptable spirometry performance acceptability/repeatability criteria

          7. Taken Ventolin on ≥2 days out of 7 days prior to Visit 2

          8. Demonstrate acceptable metered dose inhaler (MDI) administration technique as assessed
             by the investigator.

          9. Able to perform acceptable and reproducible peak expiratory flow measurements as
             assessed by the investigator

        Exclusion Criteria:

          1. Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic
             bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or
             bronchopulmonary dysplasia)

          2. Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months
             before Visit 1

          3. Chronic (≥3 weeks) use of SCS within 6 months prior to Visit 1

          4. Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab) or
             investigational biologic within 3 months or 5 half-lives before Visit 1, whichever is
             longer, or any other prohibited medication

          5. 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)

          6. Life-threatening asthma defined as any history of significant asthma episode(s)
             requiring admission to an intensive care unit, intubation associated with hypercapnia,
             respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within 5
             years of Visit 1

          7. Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1

          8. Upper respiratory infection involving antibiotic treatment not resolved within 7 days
             prior to Visit 1

          9. Hospitalizations due to asthma within 6 months prior to Visit 1

         10. Have taken ≥12 actuations per day of Sponsor-provided Ventolin during the run-in
             period prior to Visit 2 according to the below criteria:

               -  ≥2 days out of 14 days of run-in

               -  ≥3 days out of 15 to 21 days of run-in

               -  ≥4 days out of 22 or more days of run-in

         11. Unable to comply with study procedures including non-compliance with diary completion
             (ie, <70% subject completion of diary assessments in the last 7 days preceding Visit 2
             or 4-times daily dosing, <80% compliance during the placebo run-in period).

         12. Historical or current evidence of a clinically significant disease

         13. Cancer not in complete remission for at least 5 years before Visit 1

         14. Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1

         15. History of psychiatric disease, intellectual deficiency, poor motivation, or other
             conditions if their magnitude is limiting informed consent validity

         16. Significant abuse of alcohol or drugs, in the opinion of the investigator