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

NCT05477108 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: D5985C00005118313
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the Pharmacokinetic (PK) and safety of BGF MDI \[Budesonide/glycopyrronium/formoterol (BGF) metered dose inhaler (MDI)\] formulated with 2 different propellants :Hydrofluoroolefin (HFO) and Hydrofluoroalkane (HFA) with oral activated charcoal in healthy subjects (male or female).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

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

Outcome Measures

Primary Outcomes (3)

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

  Bioequivalence (Cmax) of the lung exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO compared with BGF MDI HFA was assessed.

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hours (h), 2 h, 4 h, 8 h, 12h and 24 hours post-dose on Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

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

  Bioequivalence (AUCinf) of the lung exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO compared with BGF MDI HFA was assessed.

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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)

  Bioequivalence (AUClast) of the lung exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO compared with BGF MDI HFA was assessed.

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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)

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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)

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)

• Terminal Rate Constant (λz)

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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)

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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)

  Pre-dose, 2 minutes, 5 minutes,10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h, 12 h and 24 hours post-dose on 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 with oral activated charcoal

EXPERIMENTAL

Subjects 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 with oral activated charcoal); Drug: Treatment B (BGF MDI HFA with oral activated charcoal)

Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator with oral activated charcoal

EXPERIMENTAL

Subjects 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 with oral activated charcoal); Drug: Treatment B (BGF MDI HFA with oral activated charcoal)

Interventions

Treatment A (BGF MDI HFO with oral activated charcoal) DRUG

Subject will receive 4 inhalations as a single dose with oral activated charcoal - 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 with oral activated charcoal; Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator with oral activated charcoal

Treatment B (BGF MDI HFA with oral activated charcoal) DRUG

Subject will received 4 inhalations as a single dose with oral activated charcoal - 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 with oral activated charcoal; Treatment B: BGF MDI HFA 160/7.2/4.8 μg ex-actuator with oral activated charcoal

Eligibility Criteria

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

You may qualify if:

• Healthy non-smoking male and/or female subjects aged 18 - 60 years with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating, confirmed at screening.
• 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 Forced expiratory volume in the first second (FEV1) ≥ 80% of the predicted normal value and an FEV1/FVC (Forced vital capacity) \> 70% regarding age, height, and ethnicity at the screening visit.
• Subjects must demonstrate proper inhalation technique and have the ability to properly use an MDI device after training.
• Provision of signed and dated, written informed consent prior to any study specific procedures.

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.
• 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.
• Any clinically significant abnormal findings in physical examination, or vital signs at screening.
• Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and HIV antibody.
• Subject has a positive RT-PCR test for SARS-CoV-2 prior to randomization.
• 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 COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated, Intensive Care Unit stay).
• Recent (within 14 days prior to admission to the Clinical Unit) exposure to someone who has COVID-19 symptoms or tested positive for SARS-CoV-2.
• Has a current occupation that involves routine exposure to potential COVID-19 patients or sources of SARS-CoV-2 infection (eg, healthcare worker).

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

Related Links

• Redacted CSR synopsis

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Charcoal; 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)

Carbon; Elements; Inorganic Chemicals; 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

+1-877-240-94 79

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: July 26, 2022
• First Posted: July 28, 2022
• Study Start: July 29, 2022
• Primary Completion: April 11, 2023
• Study Completion: April 11, 2023
• Last Updated: August 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-08

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 rerefer 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)