A Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, & Formoterol (BGF) Metered Dose Inhaler (MDI) Hydrofluoroolefin (HFO) With a Spacer (Treatment B), BGF MDI Hydrofluoroalkane (HFA) With a Spacer (Treatment A), as Well as BGF MDI HFO Without a Spacer (Treatment C)

Healthy Clinical Trial

Official title:

A Phase I, Randomized, Partial Double-blind, Single Dose, 3 Way Cross Over Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol for BGF MDI HFO Compared With BGF MDI HFA Using an AeroChamber Plus Flow Vu Spacer and to Compare the Lung Exposure of BGF MDI HFO With a Spacer to BGF MDI HFO Without a Spacer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06340581
• Other study ID #: D5985C00009
• Secondary ID: 2023-509914-12
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: October 17, 2024
• Est. completion date: February 27, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is a Phase I, randomized, partial double-blind, single dose, single-center, 3-way cross over study to assess the pharmacokinetic (PK) and safety of BGF MDI in healthy participants (male or female).

The study will comprise:

1. A Screening Period of up to 27 days prior to first dosing.

2. Three treatment periods: Participants will be resident at the Clinical Unit from Day -1 until 24 hours after dosing with the final treatment.

3. Follow-up: A final Follow-up Phone Call within 5 to 7 days after the last administration of BGF MDI in Treatment Period 3.

Participants will receive all 3 treatments as a single dose (4 inhalations) (Treatment A [BGF MDI HFA with AeroChamber Plus Flow-Vu spacer with charcoal, reference formulation], Treatment B [BGF MDI HFO with AeroChamber Plus Flow-Vu spacer with charcoal - test formulation], and Treatment C [BGF MDI HFO without spacer with charcoal]) (1 treatment per treatment period) in one of 6 possible treatment sequences; ABC, ACB, BAC, BCA, CAB, or CBA.

There will be a 3 to 7 days washout period between each dose administration.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 132
• Est. completion date: February 27, 2025
• Est. primary completion date: February 27, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

• Known or suspected history of drug abuse, as judged by the investigator.

• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days or 5 half-lives (whichever is longest) of the first administration of IMP in this study.

• Plasma donation within one 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 to drugs with a similar chemical structure or class to BGF or to its excipients, such as norflurane.

• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.

• Positive screen for drugs of abuse or cotinine at screening or on admission to the Clinical Unit or positive screen for alcohol at screening or on admission to the Clinical Unit.

• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.

• Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.

• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the investigator. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for women.

• Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate).

• Participants who have previously received BGF MDI HFO.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Treatment A: BGF MDI HFA
Participants will receive 4 oral inhalations of BGF MDI HFA as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.
• Treatment B: BGF MDI HFO
Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.
• Treatment C: BGF MDI HFO
Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose without spacer with charcoal.

Device:
• AeroChamber Plus Flow-Vu Spacer
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.

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast)	The relative lung bioavailability of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer versus BGF MDI HFO without a spacer will be assessed.	Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Secondary	Maximum Observed Concentration (Cmax)	The relative lung bioavailability of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer versus BGF MDI HFO without a spacer will be assessed.	Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Time to Reach Maximum Observed Concentration (tmax)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Terminal Rate Constant (?z)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Half-life Associated with Terminal Slope (?z) of a Semi-logarithmic Concentration-time Curve (t1/2?z)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Mean Residence Time of the Unchanged Drug in the Systemic Circulation from Zero to Infinity (MRTinf)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Apparent Volume of Distribution at Steady State Following Extravascular Administration (Vz/F)	The lung exposure PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and 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	Number of Participants with Adverse Events	The safety and tolerability of single doses of BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer, in healthy participants will be evaluated.	From Baseline up to 48 days