This study aims to assess the effect on total systemic exposure and to characterize exposure BGF MDI HFO with a spacer compared to without a spacer; also, to demonstrate that total systemic exposure of BGF when administered as MDI HFO with a spacer is not greater than BGF MDI HFA with a spacer.
This is a Phase I, randomized, partial double-blind, single dose, three way cross-over study to assess the effect of total systemic exposure of BGF when administered as BGF MDI HFO compared with BGF MDI HFA Using an AeroChamber Plus Flow-Vu Spacer and to compare the Total Systemic Exposure of BGF MDI HFO with a Spacer to BGF MDI HFO without a Spacer in healthy participants (male or female). The study will comprise of: * A Screening Period of up to 27 days prior to first dosing. * 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. * 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 \[BGF MDI HFA with AeroChamber Plus Flow-Vu spacer - reference formulation\], Treatment B \[BGF MDI HFO with AeroChamber Plus Flow-Vu spacer - test formulation\], and Treatment C \[BGF MDI HFO without spacer\]) (1 treatment per treatment period) in one of 6 possible treatment sequences; ABC, ACB, BAC, BCA, CAB, or CBA.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
Participants will receive 4 inhalations of BGF MDI HFA as a single dose with AeroChamber Plus Flow-Vu spacer.
Participants will receive 4 inhalations of BGF MDI HFO as a single dose with AeroChamber Plus Flow-Vu spacer.
Participants will receive 4 inhalations of BGF MDI HFO as a single dose without spacer.
Participants will receive 4 inhalations of BGF MDI HFA (Treatment A) and BGF MDI HFO (Treatment B) as a single dose with spacer.
Research Site
Berlin, Germany
Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast) of BGF MDI
To assess that the total systemic exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with AeroChamber Plus Flow-Vu spacer does not exceed that with BGF MDI HFA with AeroChamber Plus Flow-Vu spacer.
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
To assess that the total systemic exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with AeroChamber Plus Flow-Vu spacer does not exceed that with BGF MDI HFA with AeroChamber Plus Flow-Vu spacer.
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)
To assess the relative bioavailability of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer versus BGF MDI HFO without a spacer.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Maximum Observed Concentration (Cmax)
To assess the relative bioavailability of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with a spacer versus BGF MDI HFO without a spacer.
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)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Time to Reach Maximum Observed Concentration (tmax)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Terminal Rate Constant (λz)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
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)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
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)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
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)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
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)
To characterize the PK parameters of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO (with and without spacer) and BGF MDI HFA with a spacer.
Time frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Number of Participants with Adverse Events
To assess 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.
Time frame: From Baseline up to 48 days
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