title: Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA-134a or CFC propellant in a broad range of doses.
abstract: The aim of the present study was to demonstrate an equivalent asthma control and safety of inhaled budesonide 200 microg unit-dose via a spacer device (Jet Spacer, Chiesi Farmaceutici S.p.A.) given with an HFA-134a or CFC propellant in stable patients treated with inhaled corticosteroids. A total number of 270 patients, 134 in the HFA-134a group and 136 in the CFC group, completed a 2-week run-in period and were then randomised to receive a daily dose of inhaled budesonide (low dose: 400 microg, medium dose: 800 microg, high dose: 1200 or 1600 microg), defined on the basis of the dose of previous inhaled steroids given twice daily for 12 weeks. Morning and evening PEFR, intake of rescue salbutamol, number of day-time and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR and MEF50) and vital signs were measured at the clinics at study entry, at the start of treatment and after 2, 4, 8 and 12 weeks thereafter. Morning serum cortisol (8.00-10.00 AM) was measured at baseline and in the final visit. Adverse events and vital signs were recorded throughout the total study period. Small increases vs. baseline for lung function (more markedly in the high-dose subsets) and significant decreases of symptoms and use of rescue salbutamol were similarly observed in both groups. Equivalence was demonstrated for the primary endpoint morning PEFR (difference between means = -1.51 l/min; 95% CI: -9.40-6.37 l/min; pre-defined limits: +/- 42.16 l/min, i.e. +/- 10% of the reference LSM) as well as for evening PEFR and FEV1, both in the ITT population or on a per-protocol basis. No statistically significant differences between groups were observed in any of the other efficacy variables. A similar proportion of drug-related adverse events was observed in the two groups, without drug-related serious events in either group. No evidence of adrenal depletion was also noted with both propellants. In conclusion, the budesonide HFA-134a formulation given with a spacer device provided an equivalent asthma control with that of a corresponding CFC product, when administered in stable patients treated with inhaled corticosteroids in a broad range of daily doses. The use of the new propellant did not modify the safety profile of inhaled budesonide.
authors.affiliation: Clinic of Phtisiopneumonology, Medical University of Lodz, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Grzelewska-Rzymowska
authors.forename: J
authors.initials: J
authors.lastname: Malolepszy
authors.forename: M
authors.initials: M
authors.lastname: de Molina
authors.forename: K
authors.initials: K
authors.lastname: Sladek
authors.forename: J
authors.initials: J
authors.lastname: Zarkovice
authors.forename: Z
authors.initials: Z
authors.lastname: Siergiejko
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000335:Aerosol Propellants / Q000008:administration & dosage; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D017402:Chlorofluorocarbons / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects; D016896:Treatment Outcome; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D019819:Budesonide; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons