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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 (MANDALA)

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ClinicalTrials.gov Identifier: NCT03769090
Recruitment Status : Completed
First Posted : December 7, 2018
Results First Posted : September 28, 2022
Last Update Posted : September 28, 2022
Sponsor:
Information provided by (Responsible Party):
Bond Avillion 2 Development LP

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Asthma Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg Drug: Albuterol sulfate metered-dose inhaler 180 μg Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 13, 2018
Actual Primary Completion Date : August 19, 2021
Actual Study Completion Date : February 7, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arms and Interventions
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Arm Intervention/treatment
Experimental: BDA MDI (PT027) 160/180 μg
Budesonide/albuterol sulfate, BDA MDI, PT027 high dose
 Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
Budesonide/albuterol sulfate combination inhalation aerosol
Experimental: BDA MDI (PT027) 80/180 μg
Budesonide/albuterol sulfate, BDA MDI, PT027 low dose
 Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg
Budesonide/albuterol sulfate combination inhalation aerosol
Active Comparator: AS MDI (PT007) 180 µg
Albuterol sulfate MDI, PT007
 Drug: Albuterol sulfate metered-dose inhaler 180 μg
Albuterol sulfate inhalation aerosol


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 β2-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 β2-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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769090


Locations
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Sponsors and Collaborators
Bond Avillion 2 Development LP
Investigators
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Study Director: Frank Albers, MD, PhD Avillion LLP
  Study Documents (Full-Text)

Documents provided by Bond Avillion 2 Development LP:
Study Protocol  [PDF] April 8, 2021
Statistical Analysis Plan  [PDF] July 30, 2021

More Information
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Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bond Avillion 2 Development LP
ClinicalTrials.gov Identifier: NCT03769090    
Other Study ID Numbers: AV003
First Posted: December 7, 2018    Key Record Dates
Results First Posted: September 28, 2022
Last Update Posted: September 28, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Albuterol
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
 Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action