A Study to Evaluate the Effect of Budesonide, Glycopyrronium, Formoterol Fumarate (BGF) Metered Dose Inhaler (MDI), Budesonide and Formoterol Fumarate (BFF) MDI and Placebo MDI on Exercise Parameters in Participants With Chronic Obstructive Pulmonary Disease (COPD). (ATHLOS)

A Double-Blind, Multicentre, Randomized, Three-Period, Three-Treatment, Cross-Over Study to Evaluate the Effect of BGF MDI, BFF MDI, and Placebo MDI on Exercise Parameters in Participants With COPD (ATHLOS)

This study will investigate the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) compared with Placebo MDI, and Budesonide and Formoterol Fumarate (BFF) MDI on isotime inspiratory capacity (IC) and exercise endurance time.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate; Drug: Treatment B: Budesonide and Formoterol Fumarate; Drug: Treatment C : Placebo

Detailed Description

This is a multicenter, three-treatment, three-period, cross-over study to assess the effect of BGF MDI vs Placebo MDI and BFF MDI in participants with COPD who have exertional breathlessness despite treatment with mono or dual COPD maintenance therapy.

Eligible participants will be randomized equally (1:1:1:1:1:1) to 1 of 6 treatment sequences. The total duration of the study for each participant will be up to 14 weeks.

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Research Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Research Site
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • Research Site
• China
  • Guangzhou, China, 510163
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Zhengzhou, China, 450000
    • Research Site
• Germany
  • Berlin, Germany, 14050
    • Research Site
  • Berlin, Germany, 12159
    • Research Site
  • Frankfurt, Germany, 60596
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Hanover, Germany, 30449
    • Research Site
  • Heidelberg, Germany, 69115
    • Research Site
  • Lübeck, Germany, 23552
    • Research Site
  • Mainz, Germany, 55128
    • Research Site
• South Korea
  • Daegu, South Korea, 42415
    • Research Site
  • Seoul, South Korea, 05030
    • Research Site
  • Seoul, South Korea, 02447
    • Research Site
• Spain
  • Benalmádena, Spain, 29630
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • London, United Kingdom, SW3 6HP
    • Research Site
  • London, United Kingdom, W1T 6AH
    • Research Site
  • Manchester, United Kingdom, M23 9GP
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
    • Tarzana, California, United States, 91356
      • Research Site
    • Torrance, California, United States, 90502
      • Research Site
  • Florida
    • Brooksville, Florida, United States, 34613
      • Research Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Research Site
    • Greenville, South Carolina, United States, 29615
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be male or female, 40 to 80 years of age inclusive, at the time of signing the informed consent.

• Participant must have:

  • a diagnosis of COPD confirmed by a post-bronchodilator Forced expiratory volume (FEV1)/ Forced vital capacity (FVC) < 0.7 at Visit 1
  • a post-bronchodilator FEV1 ≥ 30% and <80% predicted normal (moderate to severe COPD) at Visit 1.
  • a score of ≥ 2 on the modified Medical Research Council at Visit 1.
  • pre-bronchodilator FRC of > 120% of predicted normal FRC values at Visit 1.
  • a constant work rate test endurance time of 3 to 8 minutes at Visit 2.
• Participant must be on a stable dose of mono-or dual inhaled maintenance COPD treatment for at least 6 weeks.
• Current or former smoker with a history of ≥ 10 pack-years of tobacco smoking
• Body mass index < 40 kg/m2.
• Male and Female participants (not applicable for female participants with non-childbearing potential) and their partners must use an acceptable method of contraception.

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.
• Historical or current evidence of a clinically significant disease
• Participants on oxygen therapy or that desaturate significantly (<82%) during exercise.
• Participants who are enrolled or entering a pulmonary rehabilitation program during the study.
• Participants who have cancer that has not been in complete remission for at least 5 years.
• Participants with a diagnosis of narrow-angle glaucoma that has not been adequately treated and/or change in vision that may be relevant, in the opinion of the investigator.
• Participants with symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the investigator, is clinically significant.
• Participants who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI or dry powder inhaler.
• Participant with resting (5 minutes) oxygen saturation SaO2 in room air ≤ 85%.
• A COPD exacerbation that requires hospitalization within 12 months prior to Visit 1 or a COPD exacerbation that requires systemic corticosteroids or antibiotics within 4 months of Visit 1.
• Participants with contraindications to cardiopulmonary exercise testing (CPET).
• Participants who have had a respiratory tract infection within 8 weeks prior to Visit 1 and/or during the screening period.
• Participants with lung lobectomy, lung volume reduction or lung transplantation.
• Unable to withhold short-acting bronchodilators for 6 hours prior to lung function testing at each study visit.
• Known history of drug or alcohol abuse within 12 months.
• Any regular recreational use of marijuana in the 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BGF MDI; Pressurized MDI fixed combination product of Budesonide 160 μg, Glycopyrronium 7.2 μg, and Formoterol Fumarate 4.8 μg per actuation.	Drug: Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate; Randomized participants will receive 2 inhalations of BGF MDI via oral inhalation twice daily (BID).
Active Comparator: BFF MDI; Pressurized MDI fixed combination product of Budesonide 160 μg and Formoterol Fumarate 4.8 μg per actuation.	Drug: Treatment B: Budesonide and Formoterol Fumarate; Randomized participants will receive 2 inhalations of BFF MDI via oral inhalation BID.
Placebo Comparator: Placebo; Placebo as pressurized inhalation suspension.	Drug: Treatment C : Placebo; Randomized participants will receive 2 inhalations of placebo MDI via oral inhalation BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in isotime Inspiratory capacity (IC)	To assess the effect of BGF MDI relative to Placebo MDI and BGF MDI relative to BFF MDI on dynamic hyperinflation in participants with COPD.	2 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in constant work rate cycle ergometry endurance time	To assess the effect of BGF MDI relative to Placebo MDI, BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on exercise endurance time in participants with COPD.	2 weeks post-treatment
Change from baseline in Isotime dyspnea (NRS)	To assess the effect of BGF MDI relative to Placebo MDI, BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on Isotime dyspnea in participants with COPD.	2 weeks post-treatment
Number of participants with serious adverse events (SAEs) and adverse event leading to discontinuation of study intervention (DAEs).	To assess the safety and tolerability of BGF MDI and BFF MDI.	2 weeks post-treatment
Change from baseline in functional residual capacity (FRC)	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on FRC in participants with COPD.	2 weeks post-treatment
Change from baseline in total lung capacity (TLC)	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on TLC in participants with COPD.	2 weeks post-treatment
Change from baseline in residual volume (RV)	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on RV in participants with COPD.	2 weeks post-treatment
Change from baseline in RV/TLC	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on RV/TLC in participants with COPD.	2 weeks post-treatment
Change from baseline in specific airway conductance (sGaw)	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on sGaw in participants with COPD.	2 weeks post-treatment
Change from baseline in static Inspiratory capacity (IC)	To assess the effect of BGF MDI relative to BFF MDI and BFF MDI relative to Placebo MDI on static IC in participants with COPD.	2 weeks post-treatment

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Actual): January 22, 2026
• Study Completion (Actual): January 22, 2026

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Metered Dose Inhalers
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amines; Alcohols; Amino Alcohols; Ethanolamines; Quaternary Ammonium Compounds; Onium Compounds; Pyrrolidines; Formoterol Fumarate; Glycopyrrolate
• Other Study ID Numbers: D5988C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No