Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler in Patients with Inadequately Controlled Asthma

Phase 1

• Conditions: Inadequately Controlled Asthma; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2021-002026-24-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-11
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 630

Inclusion Criteria

1. 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.

2. Participants who have a documented history of physician-diagnosed asthma = 6 months prior to Visit 1, according to GINA guidelines [GINA 2020]. Healthcare records for one year prior to Visit 1 must be provided for adolescent participants (12 to < 18 years of age) to ensure consistent evaluation and follow-up of treatment in those participants.

3. Participants who have been regularly using a stable daily ICS or an ICS/LABA regimen (including a stable ICS dose), with the ICS doses, for at least 8 weeks prior to Visit 1.

4. ACQ-7 total score = 1.5 at Visits 1 and 4.

5. Pre-bronchodilator/pre-dose FEV1 <90% predicted normal value at Visits 1, 2 and 3, and a pre-dose FEV1 of 50% to 90% at Visit 4 (pre-randomization).

6. Reversibility to albuterol, defined as a post-albuterol increase in FEV1 of = 12% and = 200 mL for participants = 18 years of age OR a postalbuterol increase in FEV1 of = 12% for participants 12 to < 18 years of age, either in the 12 months prior to Visit 1 or at Visit 2 or Visit 3.

7. A pre-bronchodilator/pre-dose FEV1 at Visits 2, 3, and 4 that have not changed 20% or more (increase or decrease) from the prebronchodilator/pre-dose FEV1 recorded at the previous visit.

8. Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment.

9. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.

10. Demonstrate acceptable MDI administration technique.

11. eDiary compliance = 70% during screening, defined as completing the daily eDiary and answering Yes to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 495
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1. Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).

2. Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the Screening Period.

3. Hospitalization for asthma within 8 weeks of Visit 1.

4. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (eg, active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, and COPD). Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety
analysis.

5. Known history of drug or alcohol abuse within 12 months of Visit 1.

6. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.

7. Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration.

8. Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).

9. Use of a nebulizer or a home nebulizer for receiving asthma medications.

10. Do not meet the stable dosing period prior to Visit 1 or unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.

11. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg, vector, lipid nanoparticle) < 7 days prior to Visit 1 (from last vaccination or booster dose).

12. Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.

13. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study.

14. Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).

15. Planned hospitalization during the study.

16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.

18. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.

19. For women only – currently pregnant (confirmed with positive highly sensitive urine pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of BFF MDI 320/9.6 µg relative to BD MDI (superiority) on lung function in participants with inadequately controlled asthma;Secondary Objective: 1. To assess the effect of BFF MDI 320/9.6 µg relative to BD MDI 320 µg (superiority) on lung function.<br><br>2. To assess the effect of BFF MDI 320/9.6 µg relative to BD MDI 320 µg on symptoms and patient reported outcomes.;Primary end point(s): 1. Europe (EU): Change from baseline in morning pre-dose trough FEV1 over 24 Weeks.;Timepoint(s) of evaluation of this end point: Europe(EU) over 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. EU (Key secondary): To assess the effect of BFF MDI 320/9.6 µg relative to BD MDI.<br><br>- Change from baseline in FEV1 AUC0-3 over 24 Weeks.<br><br>2. To assess the effect of BFF MDI 320/9.6 µg relative to BD MDI and Symbicort TBH on lung function, symptoms, and PROs.<br><br>- Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks.<br><br>- Percentage of responders in ACQ-7 (= 0.5 decrease equals response) over 24 Weeks.<br><br>- Percentage of responders in ACQ-5 (= 0.5 decrease equals response) over 24 Weeks.<br><br>- Percentage of responders in the AQLQ(s)+12 (= 0.5 increase equals response) over 24 Weeks.<br><br>- Percentage of responders in AQLQ(s)+12 (= 0.5 increase equals response) over 12 to 24 weeks.<br><br>- Onset of action on Day 1: Absolute change in FEV1 at 5 minutes postdose on Day 1.;Timepoint(s) of evaluation of this end point: As listed for each endpoint.