ATHLOS: 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).

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06067828

Collaborator

(none)

180

Enrollment

Locations

Arms

22.5

Anticipated Duration (Months)

6.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate Drug: Treatment B: Budesonide and Formoterol Fumarate Drug: Treatment C : Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Oct 13, 2023

Anticipated Primary Completion Date :

May 13, 2025

Anticipated Study Completion Date :

Aug 29, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change from baseline in isotime IC [2 weeks post-treatment]
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.

Secondary Outcome Measures

Change from baseline in constant work rate cycle ergometry endurance time [2 weeks post-treatment]
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.
Change from baseline in Isotime dyspnea (NRS) [2 weeks post-treatment]
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.
Change from baseline in resting IC (using spirometry) [2 weeks post-treatment]
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 resting IC in participants with COPD.
Change from baseline in end exercise IC [2 weeks post-treatment]
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 end exercise IC in participants with COPD.
Change from baseline in end exercise dyspnea (NRS) [2 weeks post-treatment]
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 end exercise dyspnea in participants with COPD.
Change from baseline in functional residual capacity (FRC) [2 weeks post-treatment]
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 FRC in participants with COPD.
Change from baseline in total lung capacity (TLC) [2 weeks post-treatment]
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 TLC in participants with COPD.
Change from baseline in residual volume (RV) [2 weeks post-treatment]
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 RV in participants with COPD.
Change from baseline in RV/TLC [2 weeks post-treatment]
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 RV/TLC in participants with COPD.
Change from baseline in specific airway conductance (sGaw) [2 weeks post-treatment]
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 sGaw in participants with COPD.
Number of participants with serious adverse events (SAEs) and adverse event leading to discontinuation of study intervention (DAEs). [2 weeks post-treatment]
To assess the safety and tolerability of BGF MDI and BFF MDI.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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%.
Hospitalization due to COPD exacerbation or Oral Corticosteroid use due to exacerbation within the 3 months prior to Visit 1.
Participants with contraindications to cardiopulmonary exercise testing (CPET).
Participants who have had a respiratory tract infection within 8 weeks prior to Visit

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Torrance	California	United States	90502
2	Research Site	Anderson	South Carolina	United States	29621
3	Research Site	Greenville	South Carolina	United States	29615
4	Research Site	Spartanburg	South Carolina	United States	29303
5	Research Site	Caba		Argentina	1426
6	Research Site	Caba		Argentina	C1280AEB
7	Research Site	Quilmes		Argentina	B1878FNR
8	Research Site	Edmonton	Alberta	Canada	T6G 2B7
9	Research Site	Sainte Foy	Quebec	Canada	G1V 4G5
10	Research Site	Berlin		Germany	12159
11	Research Site	Berlin		Germany	14050
12	Research Site	Frankfurt		Germany	60596
13	Research Site	Großhansdorf		Germany	22927
14	Research Site	Hannover		Germany	30449
15	Research Site	Heidelberg		Germany	69115
16	Research Site	Lübeck		Germany	23552
17	Research Site	Mainz		Germany	55128
18	Research Site	Seoul		Korea, Republic of	02447
19	Research Site	Seoul		Korea, Republic of	05030
20	Research Site	Madrid		Spain	28007
21	Research Site	Santiago de Compostela		Spain	15706
22	Research Site	Sevilla		Spain	41013
23	Research Site	Leeds		United Kingdom	LS9 7TF
24	Research Site	Leicester		United Kingdom	LE1 5WW
25	Research Site	London		United Kingdom	SW3 6HP
26	Research Site	London		United Kingdom	W1T 6AH