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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Combination product: BGF; Combination product: GFF

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Erpent, Belgium, 5101
    • Research Site
• Netherlands
  • Eindhoven, Netherlands, 5623 EJ
    • Research Site
  • Groningen, Netherlands, 9713 GZ
    • Research Site
  • Zutphen, Netherlands, 7207 AE
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Subjects who cannot perform acceptable spirometry, i.e., meet ATS/ERS acceptability criteria.
  2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BGF-GFF; Subject first treated with Budesonide/Glycopyrronium/Formoterol Fumarate followed by a washout period then treated with Glycopyrronium/Formoterol Fumarate	Combination product: BGF; Treatment with Budesonide/Glycopyrronium/FormoterolFumarate; Combination product: GFF; Treatment with Glycopyrronium/Formoterol Fumarate
Experimental: GFF-BGF; Subject first treated with Glycopyrronium/Formoterol Fumarate followed by a washout period then treated with Budesonide/Glycopyrronium/Formoterol Fumarate	Combination product: BGF; Treatment with Budesonide/Glycopyrronium/FormoterolFumarate; Combination product: GFF; Treatment with Glycopyrronium/Formoterol Fumarate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• van den Berge M, De Backer J, Van Holsbeke C, De Backer W, Trivedi R, Jenkins M, Dorinsky P, Aurivillius M. Functional respiratory imaging assessment of budesonide/glycopyrrolate/formoterol fumarate and glycopyrrolate/formoterol fumarate metered dose inhalers in patients with COPD: the value of inhaled corticosteroids. Respir Res. 2021 Jul 1;22(1):191. doi: 10.1186/s12931-021-01772-2.

Helpful Links

• Statistical Analysis Plan (SAP)
• CSP

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2019
• Primary Completion (Actual): November 11, 2019
• Study Completion (Actual): November 11, 2019

Study Registration Dates

• First Submitted: September 24, 2018
• First Submitted That Met QC Criteria: February 8, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D5980C00019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes