Budesonide/glycopyrronium/formoterol inhaler versus placebo for heart and lung function in COPD with hyperinflation

A Randomised, Double-blind, Multi-centre, Placebo-controlled, Crossover Study to Assess the Effect of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler on Cardiac and Lung Function in Participants With Chronic Obstructive Pulmonary Disease and Hyperinflation

We will test whether a combination inhaler (budesonide/glycopyrronium/formoterol) improves heart and lung function in people with COPD who have lung hyperinflation.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 40 Years to 80 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 7 sites (Ahrensburg and 6 other locations)
• Trial ID: NCT07073950 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled, crossover Phase IV study gives adults with COPD and documented hyperinflation two 21-day treatment periods of either the combination BGF metered-dose inhaler or matching placebo, with participants switching treatments in the second period. After screening and baseline assessments, cardiac and pulmonary function tests are performed before and after each treatment period to compare effects on heart performance and lung deflation. Eligible participants are current or former smokers on maintenance inhaled COPD therapy who meet spirometric and hyperinflation criteria. The trial is multicenter and includes a follow-up visit after the crossover periods.

Who should consider this trial

Good fit: Ideal candidates are adults with COPD who are current or former smokers (≥10 pack-years), have airflow obstruction (FEV1/FVC < 0.7 and pre-bronchodilator FEV1 < 80%), documented hyperinflation (FRC > 135% predicted), blood eosinophils < 300 cells/mm3, and are on maintenance inhaled COPD therapy.

Not a fit: People without lung hyperinflation, with very severe airflow obstruction (post-bronchodilator FEV1 < 30% predicted), with a history of high eosinophil counts (>300 cells/mm3), or those not using maintenance inhaled therapy may be less likely to benefit from this intervention.

Why it matters

Potential benefit: If effective, the inhaler could reduce lung hyperinflation and improve breathing and heart function in people with COPD, potentially reducing symptoms and improving daily activity.

How similar studies have performed: Other triple-combination inhalers have shown improved lung function and fewer exacerbations in COPD, but specific benefits for cardiac function in patients with hyperinflation are not well established.

Eligibility criteria

Key Inclusion Criteria:

* Current or former smoker with a history of ≥ 10 pack-years of tobacco smoking.
* A diagnosis of COPD confirmed by a post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 0.7.
* At Visit 1: A pre-bronchodilator FEV1 \< 80%.
* At Visit 1: Peripheral blood eosinophil count \< 300 cells/cubic millimeter (mm³), with no recorded history of eosinophil count \> 300 cells/mm³ in the past 12 months.
* At Visit 1: Modified Medical Research Council (mMRC) ≥ 1.
* At Visit 2: A pre-bronchodilator functional residual capacity (FRC) of \> 135% of predicted normal FRC.
* At Visit 2: A post-bronchodilator FEV1 ≥ 30% and \< 80% of the predicted normal value.
* Participants must be on mono-, dual-, or triple-inhaled maintenance COPD treatment.
* Female participants must either be not of childbearing potential or using a form of highly effective birth control.
* All women of child bearing potential must have a negative pregnancy test at the Visit 1.

Exclusion Criteria:

* A current diagnosis of asthma, asthma-COPD overlap, or any other chronic respiratory disease other than COPD, such as alpha-1 antitrypsin deficiency, active tuberculosis, lung cancer, lung fibrosis, sarcoidosis, interstitial lung disease, and pulmonary hypertension.
* History of a COPD exacerbation that required hospitalisation, or 2 or more COPD exacerbations that required systemic corticosteroids.
* History of myocardial infarction or acute coronary syndrome.
* History or current clinically significant atrial or ventricular arrhythmia to be confirmed by electrocardiogram (ECG).
* Participants with a cardiac implantable electronic device, including pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy.
* Participants with ECG QTcF interval at Visit 1 \> 460 milliseconds (ms) for males and \> 480 ms for females.
* Participants who have had a respiratory tract infection within 8 weeks prior to Visit 1 and/or during the screening/run-in period.
* Participants with lung lobectomy, lung volume reduction (during the study and within 3 months of Visit 1), or lung transplantation.

Where this trial is running

Ahrensburg and 6 other locations

• Research Site — Ahrensburg, Germany (Not_yet_recruiting)
• Research Site — Berlin, Germany (Recruiting)
• Research Site — Frankfurt, Germany (Not_yet_recruiting)
• Research Site — Hanover, Germany (Recruiting)
• Research Site — Harefield, United Kingdom (Withdrawn)
• Research Site — London, United Kingdom (Recruiting)
• Research Site — Manchester, United Kingdom (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Chronic Obstructive Pulmonary Disease; Hyperinflation; Metered Dose Inhalers; Inhaled Corticosteroid; Long-acting muscarinic antagonist; Long-acting beta2 agonist