Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo‐controlled, crossover study

Abstract

BackgroundIn response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pM DI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA-based formulations to enable an easy transition from CFC to HFA inhalers. ObjectivesThe aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 m g of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland). MethodsThis was a double blind, double dummy, randomized, placebo-controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV 1 ] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV 1 (PD 20 ) 90 min post dose. Bronchodilation was assessed with spirometry (FEV 1 , FVC, FEF ) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose. ResultsThe three formoterol formulations demonstrated significant ( P £ 0.05) improvements in bronchoprotection compared to placebo and non-inferiority of the H FA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD 20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD 20 doubling dose between HFA and (a) DPI was -0.28 (95% CI -0.84-0.29, P = 0.57) (b) CFC was -0.28 (95% CI -0.84-0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82-1.94, C. M. Houghton et al. 36058 :4 Br J Clin Pharmacol

Pharmacokinetics of budesonide and formoterol administered via a series of single‐drug and combination inhalers: four open‐label, randomized, crossover studies in healthy adults

“…Systemic exposure (AUC) to formoterol from the combination pMDI was about 20% lower than that from the formoterol DPI. In contrast, Houghton and colleagues reported similar systemic absorption of formoterol with both pMDI and DPI administration, resulting in similar systemic effects [31].…”

Bioequivalence of Two Formulations of Salmeterol Xinafoate/Fluticasone Propionate HFA pMDI in Healthy Volunteers

“…It has been shown that the same doses of a test and reference product which have comparable systemic exposure profiles also have comparable efficacy profiles [18]. However even when significant difference in the PK profiles are present when the same doses of a test and reference product are administered, no appreciable clinical differences are observed [19,20].…”

Retrospective Observations on the Ability to Diagnose and Manage Patients with Asthma through the Use of Impulse Oscillometry: Comparison with Spirometry and Overview of the Literature

“…Previously, IOS has been regarded as equivalent but not as an alternative to spirometry [4, 6]. Marotta et al showed that, for children at risk for asthma, IOS is a better predictor than spirometry [16].…”