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

Asthma Clinical Trial

— DENALI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03847896
• Other study ID #: AV004
• Secondary ID: 2018-003674-27
• Status: Completed
• Phase: Phase 3
• Start date: March 20, 2019
• Est. completion date: July 20, 2021

Study information

• Verified date: April 2023
• Source: Bond Avillion 2 Development LP
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1001
• Est. completion date: July 20, 2021
• Est. primary completion date: July 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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 ß2-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

Related Conditions & MeSH terms

• Asthma

Intervention

Combination Product:
• Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 µg (high dose)
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 metered dose inhaler / BDA MDI 80/180 µg (low dose)
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)

Drug:
• Budesonide metered dose inhaler / BD MDI 160 µg
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 metered dose inhaler / AS MDI 180 µg
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)

Other:
• Placebo metered-dose inhaler / Placebo MDI
Placebo pressurized metered dose inhaler (Placebo MDI), given as 2 inhalations of Placebo MDI, four times a day (QID)

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Santa Fe
Argentina	Research Site	Tucumán
Czechia	Research Site	Brandýs Nad Labem
Czechia	Research Site	Kralupy Nad Vltavou
Czechia	Research Site	Lovosice
Czechia	Research Site	Neratovice
Czechia	Research Site	Praha
Czechia	Research Site	Rokycany
Czechia	Research Site	Varnsdorf
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Dortmund
Germany	Research Site	Frankfurt
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Hessen
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Marburg
Germany	Research Site	Munich
Germany	Research Site	Neu Isenburg
Germany	Research Site	Sachsen
Germany	Research Site	Schleswig
Germany	Research Site	Wiesbaden
Germany	Research Site	Witten
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Serbia	Research Site	Sremska Kamenica
Serbia	Research Site	Valjevo
Slovakia	Research Site	Žilina
Slovakia	Research Site	Košice
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivs'k
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kherson
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Luts'k
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
United States	Research Site	Austin	Texas
United States	Research Site	Aventura	Florida
United States	Research Site	Bakersfield	California
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Boerne	Texas
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbia	Missouri
United States	Research Site	Corsicana	Texas
United States	Research Site	Costa Mesa	California
United States	Research Site	Dallas	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Encinitas	California
United States	Research Site	Erie	Pennsylvania
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Flint	Michigan
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Gainesville	Florida
United States	Research Site	Greenacres City	Florida
United States	Research Site	Greenfield	Wisconsin
United States	Research Site	Huntington Beach	California
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Lancaster	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Medford	Oregon
United States	Research Site	Meridian	Idaho
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Missoula	Montana
United States	Research Site	Mobile	Alabama
United States	Research Site	Monroe	North Carolina
United States	Research Site	Morgantown	West Virginia
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	Newport Beach	California
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Oviedo	Florida
United States	Research Site	Palmetto Bay	Florida
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rochester Hills	Michigan
United States	Research Site	Rolla	Missouri
United States	Research Site	Roseville	California
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Jose	California
United States	Research Site	Sherman	Texas
United States	Research Site	Skillman	New Jersey
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Toms River	New Jersey
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Warrensburg	Missouri
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Waterbury	Connecticut
United States	Research Site	White Marsh	Maryland
United States	Research Site	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Bond Avillion 2 Development LP

Countries where clinical trial is conducted

United States,  Argentina,  Czechia,  Germany,  Serbia,  Slovakia,  Ukraine, 

References & Publications (1)

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-b — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Lung function will be measured by spirometry. Baseline FEV1 will be taken as the average of the 60- and 30-minute pre-dose spirometry measures on or before randomization. Starting with the first study drug dose at Week 0 and then at Week 12, spirometry assessments will be completed at 60 and 30 minutes before the morning dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after dosing. FEV1 AUC0-6 hours will be calculated for changes from baseline (randomization visit) using the trapezoidal rule and will be normalized by dividing by the time (in hours) from dosing to the last measurement included (typically 6 hours).	Baseline and 12 weeks
Primary	Change From Baseline in Trough FEV1	Trough FEV1 is calculated at each clinic visit as the average of the 30- and 60-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 30- and 60-minute pre-dose measures collected on the day of randomization.	Baseline and 12 weeks
Secondary	Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1	The time to onset is defined as the time (minutes) from the first inhalation of randomized treatment (Day 1) to the first instance where a percentage change from baseline in FEV1 of at least 15% is observed. Participants were only to be included in the analysis if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment time point. Baseline FEV1 is defined as the average of the 30- and 60- minute pre-dose spirometry measures taken at randomization.	From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1).
Secondary	Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1	The duration of onset is defined as the time (minutes) of the continual period in which a percentage increase change from baseline in FEV1 of at least 15% is observed. Participants will only be included in the analyses if a percent change from baseline of at least 15% is observed within a nominal 30 minutes post dose assessment. If a participant has multiple periods of onset, only the first will contribute to the summary. Duration of onset can last up to the last assessment during a nominal 6 hour serial spirometry profile. Baseline FEV1 is defined as the average of the 60- and 30- minute pre-dose spirometry taken at randomization.	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).
Secondary	Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12.	A responder is defined as a participant who achieves a reduction from baseline in overall ACQ-7 score of at least 0.5. The ACQ-7 has 7 questions, with each question using a 7 point scale, where 0 = totally controlled and 6 = extremely poorly controlled. The overall ACQ-7 score is defined as the averaged score across the 7 questions. The analysis only includes participants who are uncontrolled at basellne, i.e. baseline ACQ-7 >= 1.5. All participants who discontinue treatment prior to Week 12 are classified as non-responders.	Baseline and 12 weeks
Secondary	Change From Baseline in Trough FEV1 at Week 1.	Trough FEV1 is calculated at each clinic visit as the average of the 60- and 30-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 60- and 30-minute pre-dose measures collected on the day of randomization.	Baseline and 1 week