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)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Treatment B: Budesonide and Formoterol Fumarate; Drug: Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate; Drug: Treatment C : Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06067828

D5988C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 171 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No 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%.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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171 participants in 3 patient groups, including a placebo group

BGF MDI

Active Comparator group

Description:

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

Treatment:

Drug: Treatment A : Budesonide, Glycopyrronium, and Formoterol Fumarate

BFF MDI

Active Comparator group

Description:

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

Treatment:

Drug: Treatment B: Budesonide and Formoterol Fumarate

Placebo

Placebo Comparator group

Description:

Placebo as pressurized inhalation suspension.

Treatment:

Drug: Treatment C : Placebo