Clinical trial NCT06067828: 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).
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Metered Dose Inhalers
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-05
Enrollment: 180
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

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%.
* 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.

Primary outcomes:
measure: Change from baseline in isotime Inspiratory capacity (IC)
timeFrame: 2 weeks post-treatment
Secondary outcomes:
measure: Change from baseline in constant work rate cycle ergometry endurance time
timeFrame: 2 weeks post-treatment
measure: Change from baseline in Isotime dyspnea (NRS)
timeFrame: 2 weeks post-treatment
measure: Change from baseline in functional residual capacity (FRC)
timeFrame: 2 weeks post-treatment
measure: Change from baseline in total lung capacity (TLC)
timeFrame: 2 weeks post-treatment
measure: Change from baseline in residual volume (RV)
timeFrame: 2 weeks post-treatment
measure: Change from baseline in RV/TLC
timeFrame: 2 weeks post-treatment
measure: Change from baseline in specific airway conductance (sGaw)
timeFrame: 2 weeks post-treatment
measure: Change from baseline in static Inspiratory capacity (IC)
timeFrame: 2 weeks post-treatment
measure: Number of participants with serious adverse events (SAEs) and adverse event leading to discontinuation of study intervention (DAEs).
timeFrame: 2 weeks post-treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Tarzana
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Brooksville
country: United States
facility: Research Site
state: Florida
city: Anderson
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Caba
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: Sainte Foy
country: Canada
facility: Research Site
state: Quebec
city: Guangzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Großhansdorf
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Benalmádena
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: