A Study to Assess the Total Systemic Exposure Bioequivalence of of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI With Next-Generation Propellant Compared With BGF MDI With HFA Propellant

NCT05569421 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D5985C00004
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate bioequivalence, pharmacokinetics, safety, and tolerability of Budesonide, Glycopyrronium and Formoterol (BGF) metered dose inhaler (MDI) formulated with hydrofluoroolefin (HFO) \[Test\] and hydrofluoroalkane (HFA) \[Reference\] in healthy participants (male or female).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Bioequivalence; Propellant; Corticosteroid; Long acting muscarine agonist (LAMA); Long acting beta agonist; Lung exposure; Healthy subjects; Inhaled corticosteroid (ICS); Long-acting β2 agonist (LABA); Next generation propellant (NGP)

Outcome Measures

Primary Outcomes (3)

• Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)

  The AUCinf of budesonide, glycopryrronium and formoterol in participants was evaluated.

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)

  The AUClast of budesonide, glycopryrronium and formoterol in participants was evaluated.

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Maximum Observed Plasma (Peak) Drug Concentration (Cmax)

  The Cmax of budesonide, glycopryrronium and formoterol in participants was evaluated.

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

Secondary Outcomes (7)

• Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)

  Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

Study Arms (2)

Treatment A: BGF MDI HFO 160/7.2/4.8 μg ex-actuator

EXPERIMENTAL

Participants will receive Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation will be administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.

Drug: Treatment A: BGF MDI HFO; Drug: Treatment B: BGF MDI HFA

Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator

EXPERIMENTAL

Participants will receive Reference formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation will be administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.

Drug: Treatment A: BGF MDI HFO; Drug: Treatment B: BGF MDI HFA

Interventions

Treatment A: BGF MDI HFO DRUG

Participants will receive 4 oral inhalations as a single dose - test formulation; administered during 1 treatment period.

Also known as: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFO

Treatment A: BGF MDI HFO 160/7.2/4.8 μg ex-actuator; Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator

Treatment B: BGF MDI HFA DRUG

Participants will receive 4 oral inhalations as a single dose - reference formulation; administered during 2 treatment periods.

Also known as: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFA

Treatment A: BGF MDI HFO 160/7.2/4.8 μg ex-actuator; Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female subjects aged 18 to 60 years with suitable veins for cannulation or repeated venepuncture.
• Females must have a negative pregnancy test, must not be lactating
• Have a Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive and weigh at least 50 kg and no more than 120 kg inclusive.
• Subjects must have a FEV1 ≥ 80% of the predicted normal value and an FEV1/FVC \> 70% regarding age, height, and ethnicity.
• Subjects must demonstrate proper inhalation technique and have the ability to properly use an MDI device after training.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate.
• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• History of narrow angle glaucoma not adequately treated and/or change in vision that may be relevant.
• History of symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the investigator, is clinically significant.
• Unresectable cancer that has not been in complete remission for at least 5 years.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at screening, as judged by the investigator.
• Any clinically significant abnormalities on 12-lead electrocardiogram (ECG)
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Subject has a positive Reverse transcriptase- Polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Subject has clinical signs and symptoms consistent with SARS-CoV-2 infection, eg, fever, dry cough, dyspnea, sore throat, fatigue, or laboratory confirmed acute infection with SARS-CoV-2.
• Subject who had severe course of Corona virus disease of 2019 (COVID-19) (extracorporeal membrane oxygenation, mechanically ventilated, Intensive Care Unit stay).
• History of any respiratory disorders such as asthma, Chronic Obstructive Pulmonary Disorder (COPD), or idiopathic pulmonary fibrosis.
• Known or suspected history of alcohol or drug abuse.
• Receipt of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to randomization.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Related Links

• Redacted CSP and SAP
• Redacted CSR synopsis

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 6, 2022
• Study Start: October 11, 2022
• Primary Completion: April 14, 2023
• Study Completion: April 14, 2023
• Last Updated: August 22, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)