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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)

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Not yet recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate
Treatment B: Budesonide and Formoterol Fumarate
Treatment C : Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring Metered Dose Inhalers

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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 1. 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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

BGF MDI

BFF MDI

Placebo

Arm Description

Pressurized MDI fixed combination product of Budesonide 160 μg, Glycopyrronium 7.2 μg, and Formoterol Fumarate 4.8 μg per actuation.

Pressurized MDI fixed combination product of Budesonide 160 μg and Formoterol Fumarate 4.8 μg per actuation.

Placebo as pressurized inhalation suspension.

Outcomes

Primary Outcome Measures

Change from baseline in isotime 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.

Secondary Outcome Measures

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.
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.
Change from baseline in resting IC (using spirometry)
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
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)
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)
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)
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)
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
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)
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).
To assess the safety and tolerability of BGF MDI and BFF MDI.

Full Information

First Posted
September 28, 2023
Last Updated
September 28, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT06067828
Brief Title
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).
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 13, 2023 (Anticipated)
Primary Completion Date
May 13, 2025 (Anticipated)
Study Completion Date
August 29, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
Metered Dose Inhalers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BGF MDI
Arm Type
Active Comparator
Arm Description
Pressurized MDI fixed combination product of Budesonide 160 μg, Glycopyrronium 7.2 μg, and Formoterol Fumarate 4.8 μg per actuation.
Arm Title
BFF MDI
Arm Type
Active Comparator
Arm Description
Pressurized MDI fixed combination product of Budesonide 160 μg and Formoterol Fumarate 4.8 μg per actuation.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo as pressurized inhalation suspension.
Intervention Type
Drug
Intervention Name(s)
Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate
Intervention Description
Randomized participants will receive 2 inhalations of BGF MDI via oral inhalation twice daily (BID).
Intervention Type
Drug
Intervention Name(s)
Treatment B: Budesonide and Formoterol Fumarate
Intervention Description
Randomized participants will receive 2 inhalations of BFF MDI via oral inhalation BID.
Intervention Type
Drug
Intervention Name(s)
Treatment C : Placebo
Intervention Description
Randomized participants will receive 2 inhalations of placebo MDI via oral inhalation BID.
Primary Outcome Measure Information:
Title
Change from baseline in isotime IC
Description
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.
Time Frame
2 weeks post-treatment
Secondary Outcome Measure Information:
Title
Change from baseline in constant work rate cycle ergometry endurance time
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in Isotime dyspnea (NRS)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in resting IC (using spirometry)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in end exercise IC
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in end exercise dyspnea (NRS)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in functional residual capacity (FRC)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in total lung capacity (TLC)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in residual volume (RV)
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in RV/TLC
Description
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.
Time Frame
2 weeks post-treatment
Title
Change from baseline in specific airway conductance (sGaw)
Description
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.
Time Frame
2 weeks post-treatment
Title
Number of participants with serious adverse events (SAEs) and adverse event leading to discontinuation of study intervention (DAEs).
Description
To assess the safety and tolerability of BGF MDI and BFF MDI.
Time Frame
2 weeks post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 1. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Research Site
City
Anderson
State/Province
South Carolina
ZIP/Postal Code
29621
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Research Site
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Research Site
City
Caba
ZIP/Postal Code
1426
Country
Argentina
Facility Name
Research Site
City
Caba
ZIP/Postal Code
C1280AEB
Country
Argentina
Facility Name
Research Site
City
Quilmes
ZIP/Postal Code
B1878FNR
Country
Argentina
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Research Site
City
Sainte Foy
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
12159
Country
Germany
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
14050
Country
Germany
Facility Name
Research Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Research Site
City
Großhansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Research Site
City
Hannover
ZIP/Postal Code
30449
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69115
Country
Germany
Facility Name
Research Site
City
Lübeck
ZIP/Postal Code
23552
Country
Germany
Facility Name
Research Site
City
Mainz
ZIP/Postal Code
55128
Country
Germany
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
02447
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05030
Country
Korea, Republic of
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Research Site
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Research Site
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
SW3 6HP
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
W1T 6AH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/

Learn more about this trial

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).

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