Assessment of Efficacy and Systemic Safety of a New Chlorofluorocarbon-Free Formulation of Inhaled Beclomethasone Dipropionate in Asthmatic Children

This study was undertaken with the objective to demonstrate clinical equivalence of a standard 400 μg/d dose of inhaled beclomethasone dipropionate (BDP) given via a new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma, Italy), in two dose-units of 50 μg and 100 μg or with the conventional chlorofluorocarbon (CFC) (Becotide™, 50 μg unit dose, Allen & Hanburys, U.K.). A total of 218 children, ages 6-16, with mild to moderate persistent asthma in a stable phase, entered a 2-week run-in period and were then assigned to a 12-week treatment with one of the three treatment tests, following a double-blind, double-dummy (100 μg-dose strength as open arm), multicenter, parallel groups design. Two hundred seven patients entered the intent-to-treat (ITT) analysis and 181 completed the study period. The following efficacy variables were daily recorded by children on a diary card: morning and evening PEFR, number of daytime and nighttime asthma attacks, number of nocturnal awakenings because of asthma, symptoms' scores and intake of salbutamol. Pulmonary function tests (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC], peak expiratory flow rate [PEFR], forced expiratory flow between 25%-75% of vital capacity [FEV_25-75], midexpiratory flow [MEF₅₀], forced expiratory flow at 25% of vital capacity [FEF₂₅] were measured at the clinic visits at -2, 0, 2, 4, 8 and 12 weeks of treatment. A blood sample for the measurement of morning cortisol was taken between 8:00 AM and 10:00 AM at the start and at the end of the treatment. Equivalence between the three treatment groups was demonstrated for the primary outcome measure morning PEFR as well as for the evening PEFR. No significant differences among the groups were observed for the other efficacy variables, except for FEV₁ and FVC (significantly higher increase in the two HFA groups than in the CFC group) and for the intake of salbutamol (non-significantly higher decrease of consumption in the CFC group). The three treatments also gave comparable results in terms of adverse drug reactions and of mean values of morning serum cortisol. No signs of marked cortisol decrease were reported in any of the three groups. The results of the present study therefore show that the new HFA-134a propellant can represent an alternative to the traditional CFCs in the delivery of 400 μg/d BDP in mild to moderate asthmatic children.