Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 μg day−1 delivered as an extrafine aerosol in adults with moderate asthma

Abstract

Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.

Special Invited Papers Section: Therapeutic Equivalence – Clinical Issues and Statistical Methodology in Noninferiority Trials

“…bo-controlled studies (e.g., in the discussion section of the publication, in 3 trials) (Guay et al, 1999;Guez et al, 1996;Saekeland and Albrecht, 1997), or included an additional placebo or 'minor control' (a treatment assumed to be inferior compared to the standard included in the actual trial) group (Aubier et al, 1999;Day et al, 2000;DuBiner et al, 1996;Dulin et al, 1998;Elfstraem et al, 1999;Farnier, Portal and Maigret, 2000;Lallemant et al, 2000;Matthys et al, 1998;Rehn et al, 1996;Sall, 2000;Singer et al, 2000). Here the median of the 'preserved' effect referred to the point estimate amounts to about 15% (data not shown), including four trials in which the irrelevance margin was even larger than that point estimate.…”

EXTRAFINE BECLOMETHASONE DIPROPIONATE BREATH‐ACTUATED INHALER (400 ΜG/Day) VERSUS BUDESONIDE DRY POWDER INHALER (800 ΜG/Day) IN ASTHMA

“…A placebo‐control design was not chosen for the study, since it was considered unethical for an asthmatic patient dependent on inhaled steroids to receive a placebo. Double‐blind studies have, however, previously demonstrated the efficacy of HFA‐BDP compared with placebo 16,17 …”

Efficacy of Beclomethasone Dipropionate HFA 200 μg Once Daily in Chronic Obstructive Pulmonary Disease and Bronchial Asthma

“…2 -4 Scintigraphic studies, in healthy volunteers as well as in patients with asthma, have shown HFA-BDP to have better deposition in the lungs and less deposition in the oropharynx, compared with CFC-BDP. 5,6 Subsequent studies have demonstrated the clinical efficacy of HFA-BDP versus placebo in steroid-naïve patients, 7,8 and in comparison with already existing substances and formulations. For example, half of the dose of HFA-BDP was as equally effective as conventional CFC-BDP 9 -12 and budesonide turbuhaler (BUD-TH), 13,14 whereas a dose equivalence was shown when compared with CFC-fluticasone.…”