Skip to main content
OpenTrials
Completed

NCT Number: NCT03769090

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

4 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female or male aged ≥4 years at the time of informed consent
  • Physician diagnosis of asthma documented for at least 1 year
  • 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 β2-adrenoreceptor agonist (LABA) with or without one additional maintenance therapy from the following: LTRA, LAMA, or theophylline
  • 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 β2-adrenoreceptor agonist (SABA)
  • 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
  • Demonstrate acceptable spirometry performance (i.e., meet American Thoracic Society/European Respiratory Society acceptability/repeatability criteria)
  • A documented history of at least 1 severe asthma exacerbation within 12 months before Visit 1
  • Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator

Exclusion criteria

  • 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)
  • Oral corticosteroid/SCS use (any dose and any indication) within 6 weeks before Visit 1
  • Chronic use of oral corticosteroids (OCS, ≥3 weeks use in 3 months prior to Visit 1)
  • Having received any marketed (e.g., omalizumab, mepolizumab, reslizumab, benralizumab) or investigational biologic within 3 months or any other prohibited medication
  • 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)
  • 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
  • Historical or current evidence of a clinically significant disease
  • Cancer not in complete remission for at least 5 years
  • Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1
  • History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity
  • Significant abuse of alcohol or drugs

Treatment and study plan

Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg

Combination Product

Budesonide/albuterol sulfate combination inhalation aerosol

Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg

Combination Product

Budesonide/albuterol sulfate combination inhalation aerosol

Albuterol sulfate metered-dose inhaler 180 μg

Drug

Albuterol sulfate inhalation aerosol

Primary outcomes

  1. Number of Participants With a Severe Asthma Exacerbation Event

    Time frame: 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.

    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.

Secondary outcomes

  1. Annualized Severe Exacerbation Rate

    Time frame: 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.

    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.

  2. Total Annualized Dose of Systemic Corticosteroid (SCS)

    Time frame: 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.

    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.

  3. Asthma Control Questionnaire-5 (ACQ-5) - Number of Participants Who Were Responders at Week 24

    Time frame: From baseline to 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.

  4. Asthma Quality of Life Questionnaire for Participants Aged 12 Years and Older (AQLQ+12) - Number of Participants Who Were Responders at Week 24

    Time frame: From baseline to 24 weeks

    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.

Sponsors and collaborators

Lead sponsor

Bond Avillion 2 Development LP

Industry

Registry information

Official study 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

Acronym: MANDALA

Important dates

Study start
2018
Primary completion
2021
Study completion
2022
First posted
Dec 7, 2018
Registry last updated
Sep 28, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.