A Study to Evaluate the Effects of BGF and GFF on Specific Image Based Airway Volumes and Resistance in Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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This is a randomised, controlled, two period cross-over, 4 weeks chronic dosing, study to evaluate the effects of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF) and Glycopyrronium/Formoterol Fumarate (GFF) on airway dimensions.

Detailed Description
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This is a randomised, controlled, two period cross-over, 4 weeks chronic dosing, study to evaluate the effects of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF), and Glycopyrronium/Formoterol Fumarate (GFF), on specific image based airway volumes and resistance in subjects with moderate to severe Chronic Obstructive Pulmonary Disease. In this study, airway dimension parameters will be calculated for each of the active compounds. This imaging methodology will allow an assessment of the extent of airway changes using a triple combination of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF) and the dual combination Glycopyrronium/Formoterol Fumarate (GFF).

Official Title
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A Randomized, Double-blind, Two Treatment, Two Period, Chronic Dosing (4 Weeks), Crossover, Multi-center Pilot Study to Evaluate the Effects of Budesonide/Glycopyrronium/Formoterol Fumarate and Glycopyrronium/Formoterol Fumarate on Specific Image Based Airway Volumes and Resistance in Subjects With Moderate to Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Combination Product: BGF
* Combination Product: GFF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be 40 years to ≤80 years of age inclusive, at the time of signing the informed consent form at Visit 1. COPD Diagnosis: Subjects with an established clinical history of COPD Screening clinical laboratory tests must be acceptable to the Investigator. Screening ECG must be acceptable to the Investigator Individual Compliance: Subjects must be willing to remain at the study center as required per protocol to complete all visit assessments Patients should be on scheduled maintenance treatment with one or more inhaled bronchodilator therapies. Exclusion Criteria: As judged by the investigator, any evidence of significant diseases other than COPD, i.e., disease or condition which, in the investigator's opinion makes it undesirable for the subject to participate in the trial. Spirometry Performance: Subjects who cannot perform acceptable spirometry, i.e., meet ATS/ERS acceptability criteria. Repeatability: Subjects who cannot perform technically acceptable spirometry in accordance with ATS repeatability criteria Cancer: Subjects who have cancer that has not been in complete remission for at least five years. Substance Abuse: Subjects, who in the opinion of the Investigator, significantly abuse alcohol or drugs Subjects who in the opinion of the investigator are unable to abstain from prohibited medications including LABA/LAMAs/ICS

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGF-GFF<br>Subject first treated with Budesonide/Glycopyrronium/Formoterol Fumarate followed by a washout period then treated with Glycopyrronium/Formoterol Fumarate | Combination Product: BGF<br>* Treatment with Budesonide/Glycopyrronium/FormoterolFumarate<br>Combination Product: GFF<br>* Treatment with Glycopyrronium/Formoterol Fumarate<br>|
| Experimental: GFF-BGF<br>Subject first treated with Glycopyrronium/Formoterol Fumarate followed by a washout period then treated with Budesonide/Glycopyrronium/Formoterol Fumarate | Combination Product: BGF<br>* Treatment with Budesonide/Glycopyrronium/FormoterolFumarate<br>Combination Product: GFF<br>* Treatment with Glycopyrronium/Formoterol Fumarate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specific Image-based Airway Volume (siVaw) | Specific image-based airway volume (SiVaw) measured in mL/L. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline. | Baseline, Day 29 | 
| Specific Image-based Airway Resistance (siRaw) | Specific image-based airway resistance (siRaw) measured in kPa∙s. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline. | Baseline, Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image-based Airway Volume (iVaw) | Image-based Airway Volume (iVaw) measured in mL. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline. | Baseline, Day 29 | 
| Image-based Airway Resistance (iRaw) | Image-based airway resistance (iRaw) measured in kPa∙s/L. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline. | Baseline, 29 Days | 
| Forced Expiratory Volume in One Second (Post-dose FEV1). | Change from baseline in Forced Expiratory Volume in One Second (Post-dose FEV1). | Baseline 29 Days | 
| Functional Residual Capacity (FRC) | Change from baseline in Functional residual capacity (FRC). | Baseline, Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD