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 (DENALI)

Avillion

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Combination Product: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose); Other: Placebo metered-dose inhaler / Placebo MDI; Combination Product: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose); Drug: Budesonide metered dose inhaler / BD MDI 160 µg; Drug: Albuterol sulfate metered dose inhaler / AS MDI 180 μg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03847896

AV004

2018-003674-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 1,001 patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,001 participants in 5 patient groups, including a placebo group

BDA MDI (PT027) 160/180 μg

Experimental group

Description:

Budesonide/Albuterol sulfate BDA MDI (PT027) high dose

Treatment:

Combination Product: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose)

BDA MDI (PT027) 80/180 μg

Experimental group

Description:

Budesonide/Albuterol sulfate BDA MDI (PT027) low dose

Treatment:

Combination Product: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose)

BD MDI (PT008) 160 µg

Active Comparator group

Description:

Budesonide BD MDI (PT008)

Treatment:

Drug: Budesonide metered dose inhaler / BD MDI 160 µg

AS MDI (PT007) 180 µg

Active Comparator group

Description:

Albuterol sulfate AS MDI (PT007)

Treatment:

Drug: Albuterol sulfate metered dose inhaler / AS MDI 180 μg

Placebo MDI

Placebo Comparator group

Description:

Placebo MDI

Treatment:

Other: Placebo metered-dose inhaler / Placebo MDI