A Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, & Formoterol (BGF) Metered Dose Inhaler (MDI) With a Next-generation Propellant (NGP) With a Spacer, BGF MDI Hydrofluoroalkane (HFA) With a Spacer, as Well as BGF MDI NGP Without a Spacer

NCT06340581 | Withdrawn Phase 1 FDA Drug FDA Device

• 2 other identifiers: D5985C000092023-509914-12
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of this study is to demonstrate the equivalence of budesonide, glycopyrronium, formoterol (BGF) metered dose inhaler (MDI) hydrofluoroolefin (HFO) with a spacer to BGF MDI hydrofluoroalkane (HFA) with a spacer. The secondary objective is to characterize BGF MDI HFO with and without a spacer.

Conditions

Healthy

Keywords

Ex-actuator; AeroChamber; Spacer; COPD with moderate to severe airflow obstruction; Long-acting beta2-agonist (LABA); Long-acting muscarinic antagonist (LAMA); Propellant; Next Generation Propellant (NGP); Inhaled Corticosteroid (ICS); Lung Exposure

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast) of BGF MDI

  The bioequivalence of the lung exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer compared with BGF MDI HFA with a spacer will be assessed.

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

• Maximum Observed Concentration (Cmax) of BGF MDI

  The bioequivalence of the lung exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer compared with BGF MDI HFA with a spacer will be assessed.

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

Secondary Outcomes (10)

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

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

• Maximum Observed Concentration (Cmax)

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

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

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

• Time to Reach Maximum Observed Concentration (tmax)

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

• Terminal Rate Constant (λz)

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

Study Arms (6)

Treatment Sequence 1: ABC

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFA with spacer (Treatment A), followed by BGF MDI HFO with spacer (Treatment B), and then BGF MDI HFO without spacer (Treatment C) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Treatment Sequence 2: ACB

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFA with spacer (Treatment A), followed by BGF MDI HFO without spacer (Treatment C), and then BGF MDI HFO with spacer (Treatment B) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Treatment Sequence 3: BAC

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFO with spacer (Treatment B), followed by BGF MDI HFA with spacer (Treatment A), and then BGF MDI HFO without spacer (Treatment C) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Treatment Sequence 4: BCA

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFO with spacer (Treatment B) followed by BGF MDI HFO without spacer (Treatment C), and then BGF MDI HFA with spacer (Treatment A) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Treatment Sequence 5: CAB

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFO without spacer (Treatment C), followed by BGF MDI HFA with spacer (Treatment A), and then BGF MDI HFO with spacer (Treatment B) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Treatment Sequence 6: CBA

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive single-dose treatments of BGF MDI HFO without spacer (Treatment C), followed by BGF MDI HFO with spacer (Treatment B), and then BGF MDI HFA with spacer (Treatment A) in 3 treatment periods with single dose (4 puffs) on Day 1 of all treatment periods.

Drug: Treatment A: BGF MDI HFA; Drug: Treatment B: BGF MDI HFO; Drug: Treatment C: BGF MDI HFO; Device: AeroChamber Plus Flow-Vu Spacer

Interventions

Treatment A: BGF MDI HFA DRUG

Participants will receive 4 oral inhalations of BGF MDI HFA as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.

Treatment Sequence 1: ABC; Treatment Sequence 2: ACB; Treatment Sequence 3: BAC; Treatment Sequence 4: BCA; Treatment Sequence 5: CAB; Treatment Sequence 6: CBA

Treatment B: BGF MDI HFO DRUG

Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.

Treatment Sequence 1: ABC; Treatment Sequence 2: ACB; Treatment Sequence 3: BAC; Treatment Sequence 4: BCA; Treatment Sequence 5: CAB; Treatment Sequence 6: CBA

Treatment C: BGF MDI HFO DRUG

Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose without spacer with charcoal.

Treatment Sequence 1: ABC; Treatment Sequence 2: ACB; Treatment Sequence 3: BAC; Treatment Sequence 4: BCA; Treatment Sequence 5: CAB; Treatment Sequence 6: CBA

AeroChamber Plus Flow-Vu Spacer DEVICE

Participants will receive 4 inhalations of BGF MDI HFA (treatment A) and BGF MDI HFO (Treatment B) as a single dose with AeroChamber Plus Flow-Vu spacer.

Treatment Sequence 1: ABC; Treatment Sequence 2: ACB; Treatment Sequence 3: BAC; Treatment Sequence 4: BCA; Treatment Sequence 5: CAB; Treatment Sequence 6: CBA

Eligibility Criteria

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

You may qualify if:

• Females must have a negative pregnancy test at screening and on admission to the Clinical Unit, must not be lactating.
• Have a body mass index (BMI) between 18 and 30 kilograms per meter square (kg/m\^2) inclusive and weigh at least 50 kilograms (kg).
• Have a FEV1 greater than or equal to (\>=) 80 percentage (%).
• Demonstrate basic understanding of how to use an MDI device with and without a spacer after receiving training.
• Participants should be fully/sufficiently vaccinated as per local definitions against severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2).

You may not qualify if:

• History or current evidence of any clinically significant disease or disorder, including endocrinological diseases, such as thyrotoxicosis, which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results through participation in the study.
• 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 or change in vision.
• 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, as judged by the investigator. Eg., Systolic blood pressure (BP) less than (\<) 90 millimeters of Mercury (mmHg) or greater than or equal to (\>=) 140 mmHg and diastolic BP \< 50 mmHg or \>=90 mmHg; Heart rate \< 50 beats per minute (bpm) or \> 90 bpm.
• Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening, as judged by the investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg) OR anti-hepatitis B core (HBc) antibody, indicative of hepatitis B, hepatitis C antibody, or human immunodeficiency virus (HIV).
• Positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 prior to randomization.
• Participant has clinical signs and symptoms consistent with Coronavirus disease 2019 (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, new smell or taste disorder or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
• Participant who had severe course of COVID-19 (ie, hospitalization, extracorporeal membrane oxygenation, or mechanically ventilated).
• 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.
• History of any respiratory disorders such as asthma, Chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Design

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

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 1, 2024
• Study Start: October 17, 2024
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: August 15, 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/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.