Formoterol Delivered via the Dry Powder Aerolizer® Inhaler Versus Albuterol MDI and Placebo in Mild-to-Moderate Asthma: A Randomized, Double-Blind, Double-Dummy Trial

Abstract

The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 microg and 24 microg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 microg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 microg, formoterol 24 microg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV1), both formoterol 12 microg and 24 microg were statistically superior to placebo at all time points on all test days (p < or = 0.017) and to albuterol at most time points on all test days (p < or = 0.001). The onset of improvement in FEV1 was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 microg, formoterol 24 microg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV1 area under the curve, percentage of predicted FEV1, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.

In VitroComparison of Two Delivery Devices for Administering Formoterol: Foradil®P and Formoterol Ratiopharm Single-Dose Capsule Inhaler

“…(8) Foradil Aerolizer delivers single 12-g doses of formoterol, and has been shown to provide effective long-term disease control in a range of patients with varying degrees of severity of asthma and COPD. (9)(10)(11)(12)(13) The Aerolizer has also been used more recently in some countries for delivery of budesonide (Miflonide Aerolizer, Novartis Pharma AG, Basel, Switzerland) and beclomethasone (Miflasone Aerolizer, Pharma AG, Basel, Switzerland). (14) The aim of the current study was to compare in vitro the particle size distribution, emitted dose and device resistance of formoterol delivered via Foradil Aerolizer device with formoterol delivered via a non-proprietary single-dose capsule inhaler.…”

Risk of mortality associated with formoterol: a systematic review and meta-analysis

“…There were six deaths identified in the AstraZeneca database which were not reported in the published manuscripts [28][29][30][31]. The cause of death in the study of PLESKOW et al [32] was stated to be cardio-respiratory; however, in the Novartis FDA submission, this was revised to ''asthma-related death''. In the report by VON BERG et al [33], the death was initially attributed to a subarachnoid haemorrhage; however, the AstraZeneca database reported the cause of death as respiratory failure/asthma related, as subsequently reported in an erratum [34].…”

“…There were nine deaths due to asthma (table 1), and 33 deaths due to other causes, of which 18 were attributed to cardiac causes (table 2) [26,[28][29][30][31][32][33][34][35][36][37][38][39]. Among the patients who died from asthma, five out of the seven patients randomised to formoterol were prescribed ICS (either as randomised or background maintenance therapy), and one out of two patients randomised to non-LABA comparator treatment was prescribed ICS (either as randomised or background maintenance therapy).…”

An evaluation of comparative treatment effects with high and low dose fluticasone propionate/formoterol combination in asthma

“…No comparable data are available for other ICS/LABA combinations such as fluticasone propionate/salmeterol or beclometasone/ formoterol. In the present study the top and bottom daily dose levels of the fluticasone/formoterol dose range were evaluated, since multiple previous studies have shown minimal pairwise differences in effect between contiguous dose levels of ICS and β2-agonist monotherapies in asthma [10][11][12][13][14][15][16].…”