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

Asthma Clinical Trial

— MANDALA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03769090
• Other study ID #: AV003
• Status: Completed
• Phase: Phase 3
• Start date: December 13, 2018
• Est. completion date: February 7, 2022

Study information

• Verified date: September 2022
• 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3132
• Est. completion date: February 7, 2022
• Est. primary completion date: August 19, 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 documented for at least 1 year

3. 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 ß2-adrenoreceptor agonist (LABA) with or without one additional maintenance therapy from the following: LTRA, LAMA, or theophylline

4. 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 ß2-adrenoreceptor agonist (SABA)

5. 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

6. Demonstrate acceptable spirometry performance (i.e., meet American Thoracic Society/European Respiratory Society acceptability/repeatability criteria)

7. A documented history of at least 1 severe asthma exacerbation within 12 months before Visit 1

8. Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator

Exclusion Criteria:

1. 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)

2. Oral corticosteroid/SCS use (any dose and any indication) within 6 weeks before Visit 1

3. Chronic use of oral corticosteroids (OCS, =3 weeks use in 3 months prior to Visit 1)

4. Having received any marketed (e.g., omalizumab, mepolizumab, reslizumab, benralizumab) or investigational biologic within 3 months 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 intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s) within 5 years of Visit 1

7. Historical or current evidence of a clinically significant disease

8. Cancer not in complete remission for at least 5 years

9. Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1

10. History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity

11. Significant abuse of alcohol or drugs

Related Conditions & MeSH terms

• Asthma

Intervention

Combination Product:
• Budesonide/albuterol sulfate metered-dose inhaler 160/180 µg
Budesonide/albuterol sulfate combination inhalation aerosol
• Budesonide/albuterol sulfate metered-dose inhaler 80/180 µg
Budesonide/albuterol sulfate combination inhalation aerosol

Drug:
• Albuterol sulfate metered-dose inhaler 180 µg
Albuterol sulfate inhalation aerosol

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	Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Florencio Varela
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Argentina	Research Site	San Miguel De Tucumán
Argentina	Research Site	San Miguel De Tucumán
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Canada	Research Site	Ajax	Ontario
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Canada	Research Site	Newmarket	Ontario
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United States	Research Site	Murray	Utah
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United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
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United States	Research Site	San Diego	California
United States	Research Site	San Francisco	California
United States	Research Site	San Jose	California
United States	Research Site	Scottsboro	Alabama
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Sheffield	Alabama
United States	Research Site	Sherman	Texas
United States	Research Site	South Burlington	Vermont
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	The Woodlands	Texas
United States	Research Site	Tomball	Texas
United States	Research Site	Toms River	New Jersey
United States	Research Site	Topeka	Kansas
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Tuscumbia	Alabama
United States	Research Site	Waco	Texas
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Waxahachie	Texas
United States	Research Site	Westminster	California
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winder	Georgia
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Bond Avillion 2 Development LP

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czechia,  Germany,  Serbia,  Slovakia,  South Africa,  Spain,  Ukraine,  United Kingdom, 

References & Publications (2)

Chipps BE, Albers FC, Reilly L, Johnsson E, Cappelletti C, Papi A. Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged =4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study. BMJ Open Respir Res. 2021 Dec;8(1). pii: e001077. doi: 10.1136/bmjresp-2021-001077. — View Citation

Papi A, Chipps BE, Beasley R, Panettieri RA Jr, Israel E, Cooper M, Dunsire L, Jeynes-Ellis A, Johnsson E, Rees R, Cappelletti C, Albers FC. Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. N Engl J Med. 2022 Jun 2;386(22):2071-2083. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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
Secondary	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