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: June 17, 2024
• Est. completion date: October 28, 2024

Study information

• Verified date: March 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 purpose of this study is to assess the bioequivalence of the lung exposure of budesonide, glycopyrronium, and formoterol administered as budesonide, glycopyrronium, formoterol (BGF) metered dose inhaler (MDI) hydrofluoroolefin (HFO) with AeroChamber Plus Flow-Vu spacer compared with BGF MDI hydrofluoroalkane (HFA) with AeroChamber Plus Flow Vu spacer And BFG MDI HFO (Spacer vs No 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, with a washout period of 3 to 7 days between each dose administration. 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 (Treatment A [BGF MDI HFA ex-actuator; as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal, reference formulation], Treatment B [BGF MDI HFO ex-actuator; as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal - test formulation], and Treatment C [BGF MDI HFO ex-actuator; as a single dose 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: October 28, 2024
• Est. primary completion date: October 28, 2024
• 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 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.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results.
• 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.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to drugs with a similar chemical structure or class to BGF.
• History of any respiratory disorders such as asthma, Chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis.
• 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 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).

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
n/a

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

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 compared with BGF MDI HFA 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 compared with BGF MDI HFA 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