Safety and pharmacokinetics of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) in healthy adult subjects of Japanese descent

Abstract

Introduction: BGF MDI, a budesonide, glycopyrronium, and formoterol fumarate dihydrate triple fixed-dose combination metered dose inhaler formulated using co-suspension delivery technology, is currently in Phase III global development for chronic obstructive pulmonary disease.

Methods: This was a Phase I, randomized, double-blind, placebo-controlled, ascending-dose, crossover study to assess the safety and pharmacokinetic profiles of two doses of BGF MDI in healthy adult subjects of Japanese descent (NCT02197975). Safety assessments included monitoring for adverse events (AEs). Pharmacokinetic parameters were assessed following a single dose and 7-days chronic dosing with BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg.

Results: Twenty subjects were randomized and included in the safety and pharmacokinetic populations; mean age 29.7 years; 65% male; and mean body mass index of 21.9 kg/m². The incidences of treatment-emergent AEs (TEAEs) were similar between treatments. All the TEAEs were mild to moderate in severity. Budesonide area under the plasma concentration-time curve from 0 to 12 h (AUC_0-12) and maximum observed plasma concentration (C_max) values were approximately double for the higher dose of BGF MDI compared with the lower dose on Day 1 and also following chronic dosing on Day 8. Glycopyrronium and formoterol AUC_0-12 and C_max values on Day 8 were comparable between the two doses of BGF MDI.

Discussion: Both doses of BGF MDI were well tolerated in healthy subjects of Japanese descent and the systemic exposure to budesonide was dose proportional for BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg. The safety and pharmacokinetics for BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg in Japanese subjects were comparable to data from previous studies in Western populations, which suggests that the safety and efficacy profile of BGF MDI should be similar in Western and Japanese subjects.

Keywords: Chronic obstructive pulmonary disease; Co-suspension delivery technology; ICS/LAMA/LABA; Japanese; Triple fixed-dose combination; Western.