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2601518 
Journal Article 
Evaluation of efficacy and safety of budesonide delivered via two dry powder inhalers 
Kerwin, EM; Pearlman, DS; de Guia, T; Carlsson, LG; Gillen, M; Uryniak, Tom; Simonson, SG 
2008 
Yes 
Current Medical Research and Opinion
ISSN: 0300-7995
EISSN: 1473-4877 
24 
5 
1497-1510 
English 
18419878 
WOS:000256189400029 
Background: The dry powder inhaler (DPI) device for budesonide inhalation powder 200 mu g (DPI-A*) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 mu g and 180 mu g; DPI-B dagger)).



Objective:Two multicenter, parallel-group, double-blind, randomized, 12-week studies compared the efficacy and safety of budesonide delivered via each DPI versus placebo, and the systemic exposure of budesonide from each device.



Methods: Asthmatic adults with mild-to-moderate asthma (N = 621) and patients 6-17 years with mild asthma (N 516) received budesonide DPI-B 360 mu g or DPI-A 400 mu g twice-daily (total daily dose 720 mu g or 800 mu g), budesonide DIPI-B 180 mu g or DPI-A 200 mu g once daily (total daily dose 180 mu g or 200 mu g), or matching placebo. Change in forced expiratory volume in 1 second (FEV1) and secondary variables (asthma symptoms, beta(2) -adrenergic agonist use, peak expiratory flow [PEF], and withdrawals due to worsening asthma) versus placebo were measured.



Results: In both studies, FEV1 significantly (p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI-B 180 mu g in adults. In the adult study, significantly (p < 0.05) greater improvements in all secondary variables occurred with all active treatments versus placebo. In the pediatric/adolescent study, improvements in AM/PM PEF were significantly (p <= 0.011) greater with twice-daily budesonide DPI-B 360 mu g versus placebo. Numerically fewer patients in all active-treatment groups withdrew due to worsening asthma versus placebo.



Adverse event profiles were similar among groups. In the pediatric/adolescent study, no significant differences in mean 24-h urine cortisol or cortisol:creatinine ratio assessments were observed between the active treatment groups and the placebo group. Although pharmacokinetic variables were generally similar across subgroups in the adult (n = 77) and pediatric/adolescent (n = 32) studies, pairwise treatment comparisons of twice-daily budesonide DPI-B 360 mu g versus DPI-A 400 mu g and once-daily budesonicle DPI-B 180 mu g versus DPI-A 200 mu g showed large variability for the area under the drug plasma concentration-time curve over the dosing interval and the maximum detected drug plasma concentration.



Conclusions: The efficacy and safety of budesonide DPI-A and DPI-B versus placebo were demonstrated across the low to medium inhaled corticosteroid dose range in children 2:6 years with very mild asthma and adolescents and adults with mild-to-moderate asthma, The study is limited by the evaluation of only two doses for each product in both studies. Additionally, the studies were not designed to test equivalence or noninferiority between the active products. Pharmacokinetic characterization was limited because of the small sample sizes. 
budesonide; drug efficacy; drug safety; dry powder inhaler; inhaled corticosteroids; pharmacokinetics