ABSTRACT
This study was undertaken to investigate whether budesonide 4001 microg twice daily (Chiesi Farmaceutici S.p.A.) given with the HFA-134a propellant is equivalent in efficacy and safety to the same dose regimen delivered with the marketed CFC product in adult asthmatics with mild to moderate persistent asthma; the effects of budesonide HFA 800 microg once daily were also studied. After a 2-week run-in, a total number of 98, 103 and 97 patients were assigned to the 12-week treatment with budesonide given with HFA or CFC twice daily (morning and evening), or HFA once daily (morning), respectively. The main outcome variable morning PEFR, as well as evening PEFR and clinical symptoms (day-time and night-time asthma attacks, number of asthma-induced night-time awakenings and overall symptoms' scores) were measured daily by patients. Other standard pulmonary function testing were measured at clinic visits. A blood sample for morning serum dosing (8.00-10.00 AM) was taken at baseline and at endpoint. Adverse events and vital signs were also recorded. Significant improvements at endpoint in morning and evening PEFR, as well as in clinic PEFR and MEF50, were observed in both the twice daily groups only. An exact proof of equivalence between HFA and CFC given twice daily was demonstrated for the primary parameters, morning PEFR (equivalence pre-defined limits were +/- 40.27 l/min, difference between means = 4.0 l/min and 95% CI -6.9-14.9) and secondary parameters as evening PEFR: (limits +/- 40.19 l/min, difference between means = 2.1 l/min and 95% Confidence interval (CI) -9.4-13.5) and FEV1 (limits +/- 0.27 l, difference between means = 0.0 l and 95% CI -0.11-0.10). Less evident (but within limits) proofs of equivalence were shown in the comparisons with the once daily group. No substantial differences between the three groups were observed for the other efficacy variables, including symptoms and use of rescue salbutamol, which significantly improved over the run-in values in all groups. Minimal and non-significant decreases over pre-treatment values were observed in the three groups for morning serum cortisol levels: the analysis of individual data has shown a better outcome in the HFA twice daily regimen, compared with the other two groups. Again, a similar amount of patients in both the twice daily groups reported drug-related adverse events, which were more frequent in the once daily HFA group. Therefore, the results of this study have shown that inhaled budesonide given with new HFA-134a propellant can replace microgram-equivalent doses of the corresponding marketed CFC product when given twice daily. An overall maintainment and an unchanged risk-benefit ratio has emerged for budesonide HFA given once daily, which was however slightly inferior compared with the standard twice daily regimens.
