Pharmacokinetic profile of beclometasone dipropionate/formoterol fumarate administered through a novel dry-powder inhaler in Chinese healthy volunteers

Introduction

An extrafine formulation of the inhaled corticosteroid beclometasone dipropionate (BDP) plus the long-acting β₂-agonist formoterol fumarate (FF) has been available for years via a pressurised metered-dose inhaler for the management of asthma and chronic obstructive pulmonary disease. More recently, the same extrafine BDP/FF formulation has become available in a multidose dry-powder inhaler (DPI) called the NEXThaler. The pharmacokinetics (PK) of BDP/FF via this DPI have previously been evaluated in a Caucasian population. The current study aimed to evaluate the PK profile of BDP/FF via DPI in healthy Chinese volunteers. The results were then compared to previous Caucasian data.

Methods

This open-label parallel group study randomised subjects to single-dose BDP/FF 200/12, 400/24, or 800/48 μg via DPI. Blood samples were taken up to 24 h post-dose for PK evaluation of BDP, beclometasone 17-monopropionate (B17MP, active metabolite of BDP) and formoterol. The primary objective of the study was to evaluate the PK of BDP/FF (BDP, B17MP and formoterol). The study is registered on the World Health Organization International Clinical Trials Registry Platform (ChiCTR1900021899).

Results

Of 36 subjects randomised, all completed the study. Following inhalation of all three doses, plasma concentration of formoterol and BDP increased rapidly, with peak mean values at the first post-dose timepoint (5 min), then rapidly decreasing; B17MP reached peak concentration slightly later. Plasma exposure to formoterol, BDP and B17MP increased broadly in a dose-proportional manner to BDP/FF dose, with t_max values similar across the dose range. All BDP/FF doses were generally well tolerated.

Conclusions

Therapeutic and supra-therapeutic doses of BDP/FF administered via DPI resulted in approximately dose-proportional plasma exposure in healthy Chinese subjects, with PK profiles that were comparable to previous data from Caucasian subjects.