Clinical trial NCT03847896: 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
Official title: A 12-week, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group, Phase III Study Evaluating the Efficacy and Safety of PT027 Compared to PT008 and PT007 Administered QID in Adults and Children 4 Years of Age or Older With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Bond Avillion 2 Development LP
Sponsor class: INDUSTRY
First posted: 2019-02-20
Enrollment: 1001
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Trough FEV1
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1
timeFrame: From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1).
measure: Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1
timeFrame: Onset up to about 40 minutes post-treatment, with duration lasting up to the last assessment of a nominal 6 hour serial spirometry profile (Day 1).
measure: Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12.
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Trough FEV1 at Week 1.
timeFrame: Baseline and 1 week
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Costa Mesa
country: United States
facility: Research Site
state: California
city: Encinitas
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
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state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
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state: California
city: Roseville
country: United States
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state: California
city: Sacramento
country: United States
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state: California
city: San Diego
country: United States
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state: California
city: San Jose
country: United States
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state: California
city: Waterbury
country: United States
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state: Connecticut
city: Aventura
country: United States
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state: Florida
city: Clearwater
country: United States
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state: Florida
city: Gainesville
country: United States
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state: Florida
city: Greenacres City
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
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state: Florida
city: Orlando
country: United States
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state: Florida
city: Oviedo
country: United States
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state: Florida
city: Palmetto Bay
country: United States
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state: Florida
city: Pembroke Pines
country: United States
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state: Florida
city: Pembroke Pines
country: United States
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state: Florida
city: Meridian
country: United States
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state: Idaho
city: Chicago
country: United States
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state: Illinois
city: Chicago
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state: Illinois
city: White Marsh
country: United States
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state: Maryland
city: Boston
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state: Massachusetts
city: North Dartmouth
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state: Massachusetts
city: Farmington Hills
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state: Michigan
city: Flint
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state: Michigan
city: Rochester Hills
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state: Michigan
city: Woodbury
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state: Minnesota
city: Columbia
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state: Missouri
city: Rolla
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state: Missouri
city: Saint Louis
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state: Missouri
city: Warrensburg
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state: Missouri
city: Missoula
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state: Montana
city: Bellevue
country: United States
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state: Nebraska
city: Bellevue
country: United States
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Las Vegas
country: United States
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state: Nevada
city: Skillman
country: United States
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state: New Jersey
city: Toms River
country: United States
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state: New Jersey
city: Bronx
country: United States
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state: New York
city: New Hyde Park
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Monroe
country: United States
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state: North Carolina
city: Raleigh
country: United States
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state: North Carolina
city: Oklahoma City
country: United States
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state: Oklahoma
city: Oklahoma City
country: United States
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state: Oklahoma
city: Tulsa
country: United States
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state: Oklahoma
city: Medford
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state: Oregon
city: Portland
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state: Oregon
city: Erie
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state: Pennsylvania
city: Warwick
country: United States
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state: Rhode Island
city: Gaffney
country: United States
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state: South Carolina
city: Spartanburg
country: United States
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state: South Carolina
city: Knoxville
country: United States
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state: Tennessee
city: Austin
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state: Texas
city: Boerne
country: United States
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state: Texas
city: Corsicana
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state: Texas
city: Dallas
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state: Texas
city: El Paso
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state: Texas
city: San Antonio
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: Sherman
country: United States
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state: Texas
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Greenfield
country: United States
facility: Research Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
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city: Buenos Aires
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Tucumán
country: Argentina
facility: Research Site
city: Brandýs Nad Labem
country: Czechia
facility: Research Site
city: Kralupy Nad Vltavou
country: Czechia
facility: Research Site
city: Lovosice
country: Czechia
facility: Research Site
city: Neratovice
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Rokycany
country: Czechia
facility: Research Site
city: Varnsdorf
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
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city: Berlin
country: Germany
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city: Berlin
country: Germany
facility: Research Site
city: Darmstadt
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hessen
country: Germany
facility: Research Site
city: Leipzig
country: Germany
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city: Lübeck
country: Germany
facility: Research Site
city: Marburg
country: Germany
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city: Munich
country: Germany
facility: Research Site
city: Neu Isenburg
country: Germany
facility: Research Site
city: Sachsen
country: Germany
facility: Research Site
city: Schleswig
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Witten
country: Germany
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Valjevo
country: Serbia
facility: Research Site
city: Košice
country: Slovakia
facility: Research Site
city: Žilina
country: Slovakia
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivs'k
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kherson
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Luts'k
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
Study officials:
affiliation: Avillion LLP
name: Frank Albers, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Chipps BE, Israel E, Beasley R, Panettieri RA Jr, Albers FC, Rees R, Dunsire L, Danilewicz A, Johnsson E, Cappelletti C, Papi A. Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial. Chest. 2023 Sep;164(3):585-595. doi: 10.1016/j.chest.2023.03.035. Epub 2023 Mar 30.