A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD

Abstract

Background: Formoterol fumarate (FF) is a well-established long-acting β2-agonist. This represents the first clinical study of FF in a metered-dose inhaler (FF MDI) based on proprietary lipid-based porous-particle engineering technology.

Methods: In this randomized, double-blind, 5-period, crossover study (NCT00880490), subjects received 2.4, 4.8, and 9.6 μg of FF MDI, open-label Foradil(®) Aerolizer(®) (FA) 12 μg, and placebo. Spirometry was performed at baseline, 15 and 30 min, and 1, 2, 4, 6, 8, 10, 11.5, and 12 h post-dose.

Results: Thirty-four subjects were enrolled. Improvement in forced expiratory volume in 1 s (FEV1) was similar between FF MDI 9.6 μg and FA. Change in FEV1 area under the curve for 0-12 h (AUC0-12) for each FF MDI dose demonstrated superior efficacy versus placebo (P < .001 for all 3 doses). Over 12 h and at each time point, FF MDI 9.6 μg was non-inferior to FA for FEV1 AUC0-12 with the 95% CI's supporting a maximum difference of approximately 45 mL. Peak and trough FEV1, forced vital capacity, peak expiratory flow rate, peak inspiratory capacity, and pharmacokinetics confirmed the primary endpoint, with dose ordering of the FF MDI 2.4, 4.8, and 9.6 μg, and comparability of FF MDI 9.6 μg to FA. All 3 doses of FF MDI were safe and well-tolerated, with a safety profile similar to that of placebo and FA.

Conclusions: The efficacy and pharmacokinetic profile of FF MDI 9.6 μg were comparable to FA 12 μg and with similar safety to placebo and FA.

Trial registration: This clinical trial was registered on ClinicalTrials.gov, Identifier: NCT NCT00880490.

Keywords: Chronic obstructive pulmonary disease; Formoterol fumarate MDI; Porous particle technology.