A Randomized, Double-Blind, Double Dummy, Parallel Group, Multicenter Variable Length Study to Assess the Efficacy and Safety of PT010 Relative to PT009 and Symbicort® in Adult and Adolescent Participants With Inadequately Controlled Asthma
Overview
- Phase
- Phase 3
- Intervention
- BGF MDI 320/28.8/9.6 μg
- Conditions
- Asthma
- Sponsor
- AstraZeneca
- Enrollment
- 2187
- Locations
- 1
- Primary Endpoint
- Rate of severe asthma exacerbations
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a variable length study to evaluate the efficacy and safety of budesonide/glycopyrronium/formoterol inhaler in adults and adolescents with severe asthma inadequately controlled with standard of care.
Detailed Description
This is a randomized, double-blind, double dummy, parallel group, multicenter 24 to 52 week variable length study to assess the efficacy and safety of budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler (MDI) relative to budesonide and formoterol fumarate MDI and Symbicort® pressurized MDI in adult and adolescent participants with inadequately controlled asthma. Approximately 2200 participants will be randomized globally.
Investigators
Eligibility Criteria
Inclusion Criteria
- •12 to 80 years of age, male and female, BMI \<40 kg/m2; females must be not of childbearing potential or using a form of highly effective birth control.
- •Documented history of physician-diagnosed asthma \> and/or = 1 year prior to V
- •Regularly using a stable daily ICS/LABA regimen (including a stable ICS dose) with medium-to-high ICS doses for at least 4 weeks prior to V
- •ACQ-7 total score ≥1.5 at Visits 1, 3, and 5 (pre-randomization).
- •FEV1 % (assessed as an average of the 60 and 30 minute pre-dose assessments) predicted normal at V1, 2, 3, 4, and 5 (pre-randomization)
- •Participants \> and/or = 18 years of age: \< 80%
- •Participants 12 to \<18 years of age: \< 90%
- •FEV1 post-albuterol at V2 or V3 (if repeat needed). • Participants \> and/or = 18 years of age: Increase \> and/or = 12% and \> and/or = 200 mL.
- •Participants 12 to \<18 years of age: Increase =12% either in the 12 months prior to Visit 1 or at Visit 2, or at Visit
- •Note: Even if there is documented history of reversibility, all participants must be assessed for reversibility at Visit 2 (and Visit 3, if reversibility is not demonstrated at Visit 2) to provide reversibility baseline data for characterization.
Exclusion Criteria
- •Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids within 4 weeks of V
- •2a. Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.
- •2b. Any marketed or investigational biologics within 3 months or 5 halflives of V1, whichever is longer and must not be used during study duration.
- •Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months prior to V1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
- •Current evidence of COPD.
- •5a. Oral and IV corticosteroid use (any dose) within 4 weeks of V
- •5b. Use of systemic corticosteroids for any other reason except for the acute treatment of severe asthma exacerbation is prohibited for the duration of the study.
- •5c. Depot corticosteroid use for any reason within 3 months of V
- •Use of LAMA, either alone or as part of an inhaled combination therapy, in the 12 weeks prior to Visit
- •Use of oral beta2-agonist within 3 months of V
Arms & Interventions
Budesonide, glycopyrronium, and formoterol fumarate (BGF) MDI 320/28.8/9.6 μg
BGF MDI 320/28.8/9.6 μg Budesonide, glycopyrronium, and formoterol fumarate (PT010) Metered Dose Inhaler (MDI)
Intervention: BGF MDI 320/28.8/9.6 μg
BGF MDI 320/14.4/9.6 μg
BGF MDI 320/14.4/9.6 μg Budesonide, glycopyrronium, and formoterol fumarate (PT010) Metered Dose Inhaler (MDI)
Intervention: BGF MDI 320/14.4/9.6 μg
Budesonide and formoterol fumarate (BFF) MDI 320/9.6 μg
BFF MDI 320/9.6 μg (Experimental/Comparator) Budesonide and formoterol fumarate (PT009) Metered Dose Inhaler (MDI)
Intervention: BFF MDI 320/9.6 μg
Symbicort®
Budesonide/ formoterol fumarate pressurized metered dose inhaler (pMDI) 320/9 μg
Intervention: BFF pMDI 320/9 μg
Outcomes
Primary Outcomes
Rate of severe asthma exacerbations
Time Frame: Up to 52 Weeks
Primary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations
Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24
Time Frame: 24 Weeks
Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24
Secondary Outcomes
- Change from baseline in morning pre-dose trough FEV1 at Week 24(24 Weeks)
- Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24(24 Weeks)
- Time to first severe asthma exacerbation(Up to 52 Weeks)
- Rate of severe asthma exacerbations for participants with percent predicted FEV1 ≤ 55% at baseline.(Up to 52 Weeks)
- Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12) (≥0.5 increase equals response) at Week 24(24 Weeks)
- Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1(Day 1)
- Time to first moderate/severe asthma exacerbation(Up to 52 Weeks)
- Percentage of responders in Asthma Control Questionnaire (ACQ)-7 (≥0.5 decrease equals response) at Week 24(24 Weeks)
- Percentage of responders in ACQ-5 (≥0.5 decrease equals response) at Week 24(24 Weeks)
- Rate of moderate/severe asthma exacerbations(Up to 52 Weeks)
- Rate of severe asthma exacerbations for participants with ≥ 1 severe exacerbation in the 12 months prior to Visit 1.(Up to 52 Weeks)