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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Participants will receive 4 oral inhalations of BGF MDI HFA as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.
Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose with AeroChamber Plus Flow-Vu spacer with charcoal.
Participants will receive 4 oral inhalations of BGF MDI HFO as a single dose without spacer with charcoal.
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.
Time frame: 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.
Time frame: 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 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.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
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.
Time frame: 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)
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.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
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.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Terminal Rate Constant (λz)
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.
Time frame: 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 (t1/2λz)
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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
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.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
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.
Time frame: From Baseline up to 48 days