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).

Chronic Obstructive Pulmonary Disease Clinical Trial

— ATHLOS  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06067828
• Other study ID #: D5988C00001
• Status: Recruiting
• Phase: Phase 3
• Start date: October 24, 2023
• Est. completion date: August 25, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: August 25, 2025
• Est. primary completion date: August 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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 ß2-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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate
Randomized participants will receive 2 inhalations of BGF MDI via oral inhalation twice daily (BID).
• Treatment B: Budesonide and Formoterol Fumarate
Randomized participants will receive 2 inhalations of BFF MDI via oral inhalation BID.
• Treatment C : Placebo
Randomized participants will receive 2 inhalations of placebo MDI via oral inhalation BID.

Locations

Country	Name	City	State
Argentina	Research Site	Caba
Argentina	Research Site	Quilmes
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Sainte Foy	Quebec
China	Research Site	Shenyang
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt
Germany	Research Site	Großhansdorf
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Lübeck
Germany	Research Site	Mainz
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Madrid
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United States	Research Site	Anderson	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  China,  Germany,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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