Assessment of the systemic effects of budesonide inhaled from Easyhaler (R) and from Turbuhaler (R) in healthy male volunteers

The main objective of this study was to show dose-dependent equivalence in the systemic activity of budesonide 800 mug day (-1) and 1600 mug day(-1) d elivered from either Easyhaler(R) or Turbuhaler(R) in healthy male subjects . This single-centre study was carried out according to a randomized, double- blind, double-dummy, five-way crossover design over a 9-week period. All su bjects received 1 week of treatment with the following, in randomized order , with a washout week between each treatment: budesonide Easyhaler(R) 800 m ug day(-1) plus placebo Turbuhaler(R); budesonide Easyhaler(R) 1600 mug day (-1) plus placebo Turbuhaler(R); placebo Easyhaler(R) plus Pulmicort(R) Tur buhaler(R) 800 mug day(-1): placebo Easyhaler(R) plus Pulmicort(R) Turbuhal er(R) 1600 mug day(-1); placebo Easyhaler(R) plus placebo Turbuhaler(R). Th e final inhalation of study drug was performed at the study centre, where b lood and urine samples were collected. Fifteen subjects were recruited and all completed the study. Mean serum cor tisol AUC(0 20) values (the primary outcome variable) were comparable for e ach device at the two dose levels, and met the defined criteria for equival ence (90% CI 0.8-1.25 for between-treatment difference). Budesonide 800 mug day(-1) caused minimal suppression of serum cortisol AUC(0-20) values. Bud esonide 1600 mug day(-1) statistically significantly suppressed serum corti sol AUC(0-20) values compared with placebo. Mean morning serum cortisol val ues were within the reference range in all treatment groups, At a budesonid e dose of 800 mug day(-1) mean urine cortisol/creatinine ratio was statisti cally significantly higher with Easyhaler(R) than with Turbuhaler(R), but t here was no significant difference between the devices at the 1600 mug day( -1) dose. Serum budesonide concentrations were equivalent for each device a t both dose levels. Adverse drug reactions were infrequent and mild in natu re and there were no clinically significant changes in laboratory safety va riables. In conclusion, in healthy male volunteers, budesonide 800 mug day(-1) and 1 600 mug day(-1) inhaled from Easyhaler(R) had comparable systemic effects t o the same doses inhaled via Turbuhaler(R). (C) 2001 Harcourt Publishers Lt d.