A Study to Investigate the Effect of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Compared With Placebo MDI on Heart and Lung Function in Participants With Chronic Obstructive Pulmonary Disease (COPD) and Hyperinflation

Official title

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

Overview

The purpose of the study is to evaluate the effect of BGF MDI compared with placebo MDI on cardiac and lung function when administered in participants diagnosed with COPD and hyperinflation.

Detailed description

This is a Phase IV, randomised, double blind, multiple centre, placebo controlled, crossover study where the effectiveness of BGF MDI in comparison with matching placebo MDI on cardiac and lung function will be evaluated in patients with COPD and hyperinflation.

The study will comprise of:

* Screening period * Participants will receive placebo inhaler and salbutamol before randomization * Two treatment periods of 21 days each, where participants will be randomized 1:1 to receive either the study intervention BGF metered-dose inhaler (MDI) or placebo in Period 1 then crossover to matching placebo or BGF in Period 2 * A final follow-up period

Interventions

• Drug Budesonide/Glycopyrronium/Formoterol Fumarate
  BGF will be administered as 2 inhalations via oral route of administration
• Drug Placebo
  Matching placebo will be administered as 2 inhalations via oral route of administration
• Device Metered dose inhaler
  Participants will receive BGF and matching placebo via metered dose inhaler in treatment periods of the study.

Primary outcome measures

• Change from baseline in left ventricular end diastolic volume indexed by body surface area (LVEDVi) measured by magnetic resonance imaging (MRI) [Time frame: Up to 3 weeks]

Secondary outcome measures (2)

• Change from baseline in functional residual capacity/total lung capacity (FRC/TLC) measured by body plethysmography [Time frame: Up to 3 weeks]
• Change from baseline in residual volume/total lung capacity (RV/TLC) measured by body plethysmography [Time frame: Up to 3 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

Germany · 4 centers

• Research Site — Ahrensburg
• Research Site — Berlin
• Research Site — Frankfurt
• Research Site — Hanover

United Kingdom · 3 centers

• Research Site — Harefield
• Research Site — London
• Research Site — Manchester

Identifiers

NCT: NCT07073950 · D5980C00048 · 2025-521987-37-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗