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

A Phase I, Randomized, Double-blind, Single-dose, Partial-replicate, 3-way Cross-over Study to Assess the Total Systemic Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Treatment A: BGF MDI HFO; Drug: Treatment B: BGF MDI HFA

Detailed Description

This is a Phase I, randomized, double-blind, single-dose, single-center, partial-replicate, 3 way cross-over study to assess pharmacokinetic and safety of BGF MDI when administered with different propellants, HFO (HFO-1234ze) - test and HFA (HFA-134a) - reference.

The study will comprise of:

• A screening period up to 28 days prior to first dosing;
• Three Treatment Periods: Participants will be resident at the Clinical Unit from the morning on the day before dosing with BGF MDI on Day -1 of Treatment Period 1, until 24 hours following the final dose on Day 2 of Treatment Period 3, with a washout period of 3 to 7 days between each dose; and
• Follow-up: final safety Follow-up Phone Call within 3 to 7 days after the last administration of BGF MDI in Treatment Period 3.

Each participant will receive 3 single dose treatments of BGF MDI (Treatment A: BGF MDI HFO [Test]; Treatment B: BGF MDI HFA [Reference]) following an overnight fast of at least 8 hours on Day 1 of each treatment period.

The reference formulation will be administered during 2 of the 3 treatment periods.

There will be a minimum of a 3 to 7 day washout between administration of each treatment.

Each participant will be involved in the study for approximately 55 days.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
• Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of IMP.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• Excessive intake of caffeine-containing drinks or food. Excessive intake of caffeine defined as the regular consumption of more than 600 mg of caffeine per day or would likely be unable to refrain from the use of caffeine-containing beverages during confinement.
• Subjects who have previously received BGF MDI HFO.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: BGF MDI HFO 160/7.2/4.8 μg ex-actuator; 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; Participants will receive 4 oral inhalations as a single dose - test formulation; administered during 1 treatment period.; Other Names: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFO; Drug: Treatment B: BGF MDI HFA; Participants will receive 4 oral inhalations as a single dose - reference formulation; administered during 2 treatment periods.; Other Names: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFA
Experimental: Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator; 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; Participants will receive 4 oral inhalations as a single dose - test formulation; administered during 1 treatment period.; Other Names: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFO; Drug: Treatment B: BGF MDI HFA; Participants will receive 4 oral inhalations as a single dose - reference formulation; administered during 2 treatment periods.; Other Names: Budesonide/Glycopyronium/Formoterol fumarate pressurized inhalation suspension, HFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)	The tmax 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)
Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)	The λz 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)
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)	The t½λz 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)
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)	The MRTinf 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)
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	The CL/F 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)
Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)	The Vz/F 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)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	The safety and tolerability of single doses of BGF MDI HFO and BGF MDI HFA was evaluated in healthy participants.	From Screening up to Follow-up (3 to 7 days post final dose) [approximately 55 days]

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Publications and helpful links

Helpful Links

• Redacted CSP and SAP
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2022
• Primary Completion (Actual): April 14, 2023
• Study Completion (Actual): April 14, 2023

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy subjects; Corticosteroid; Long acting muscarine agonist (LAMA); Long acting beta agonist; Propellant; Lung exposure; Inhaled corticosteroid (ICS); Long-acting β2 agonist (LABA); Next generation propellant (NGP)
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neurotransmitter Agents; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate; Budesonide
• Other Study ID Numbers: D5985C00004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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. All request 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 shared.

• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No