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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 : Recruiting
First Posted : December 7, 2018
Last Update Posted : November 28, 2019
Sponsor:
Information provided by (Responsible Party):
Bond Avillion 2 Development LP

Tracking Information
First Submitted Date  ICMJE November 30, 2018
First Posted Date  ICMJE December 7, 2018
Last Update Posted Date November 28, 2019
Actual Study Start Date  ICMJE December 27, 2018
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
Time to first severe asthma exacerbation [ Time Frame: until 570 total first severe asthma exacerbation events have occurred and all subjects have been assessed for at least 24 weeks after starting treatment ]
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 1 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03769090 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • Severe exacerbation rate (annualized) [ Time Frame: until 570 total first severe asthma exacerbation events have occurred and all subjects have been assessed for at least 24 weeks after starting treatment ]
    The annualized exacerbation rate is based on exacerbations reported in the Asthma Exacerbation eCRF
  • Total corticosteroid exposure over the treatment period [ Time Frame: until 570 total first severe asthma exacerbation events have occurred and all subjects have been assessed for at least 24 weeks after starting treatment ]
    Total corticosteroid exposure reported as the mean daily dose will be calculated for each subject as the sum of the cumulative doses of maintenance inhaled corticosteroids, reliever inhaled corticosteroids, prescribed inhaled corticosteroids, and systemic corticosteroids divided by the number of days the subject was in the study prior to treatment discontinuation.
  • Asthma Control Questionnaire-5 (ACQ-5) change from baseline at Week 24 [ Time Frame: 24 weeks ]
    Change from baseline in ACQ-5 as compared to albuterol sulfate 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) is the mean of the 5 symptom items.
  • Asthma Control Questionnaire-5 (ACQ-5) responder analysis at Week 24 [ Time Frame: 24 weeks ]
    ACQ-5 responders as compared to albuterol sulfate at Week 24. ACQ-5 responders are defined as subjects achieving a decline from baseline of at least 0.5 on the ACQ-5.
  • Asthma Quality of Life Questionnaire (AQLQ) for 12 years and older/Pediatric Asthma Quality of Life Questionnaire (PAQLQ) change from baseline at Week 24 [ Time Frame: 24 weeks ]
    AQLQ consists of 32 questions in 4 domains and PAQLQ consists of 23 questions in 3 domains. Both are 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. As the PAQLQ is not validated for children less than 7 years of age, data for subjects who are aged 4 to 6 years will be excluded from the analyses of PAQLQ endpoints.
  • Asthma Quality of Life Questionnaire (AQLQ) for 12 years and older/Pediatric Asthma Quality of Life Questionnaire (PAQLQ) responder analysis at Week 24 [ Time Frame: 24 weeks ]
    Responders at Week 24 are defined as subjects achieving an increase from baseline of at least 0.5 on the AQLQ or PAQLQ
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg
    Budesonide/albuterol sulfate combination inhalation aerosol
  • Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
    Budesonide/albuterol sulfate combination inhalation aerosol
  • Combination Product: Albuterol sulfate metered-dose inhaler 180 μg
    Albuterol sulfate inhalation aerosol
Study Arms  ICMJE
  • Experimental: BDA MDI (PT027) 80/180 μg
    BDA MDI (PT027) low dose
    Intervention: Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/180 μg
  • Experimental: BDA MDI (PT027) 160/180 μg
    BDA MDI (PT027) high dose
    Intervention: Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
  • Active Comparator: AS MDI (PT007) 90 µg
    Intervention: Combination Product: Albuterol sulfate metered-dose inhaler 180 μg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 6, 2018)
3100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Piotr Bernat, PharmD 48 22 219 5184 piotr.bernat@syneoshealth.com
Listed Location Countries  ICMJE Argentina,   Canada,   Czechia,   Germany,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03769090
Other Study ID Numbers  ICMJE AV003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bond Avillion 2 Development LP
Study Sponsor  ICMJE Bond Avillion 2 Development LP
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bond Avillion 2 Development LP
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP