title: Evaluation of efficacy and safety of budesonide delivered via two dry powder inhalers.
abstract: BACKGROUND
  The dry powder inhaler (DPI) device for budesonide inhalation powder 200 microg (DPI-A) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 microg and 180 microg; DPI-B).
  
  
  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 microg or DPI-A 400 microg twice-daily (total daily dose 720 microg or 800 microg), budesonide DPI-B 180 microg or DPI-A 200 microg once daily (total daily dose 180 microg or 200 microg), or matching placebo. Change in forced expiratory volume in 1 second (FEV(1)) 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, FEV(1) significantly (p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI-B 180 mug 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 <or= 0.011) greater with twice-daily budesonide DPI-B 360 microg 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 microg versus DPI-A 400 microg and once-daily budesonide DPI-B 180 microg versus DPI-A 200 microg 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 >or= 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.
authors.affiliation: Clinical Research Institute of Southern Oregon, Medford, OR 97504, USA. ekerwin@criresearch.com
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.forename: David S
authors.initials: DS
authors.lastname: Pearlman
authors.forename: Teresita
authors.initials: T
authors.lastname: de Guia
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Carlsson
authors.forename: Michael
authors.initials: M
authors.lastname: Gillen
authors.forename: Tom
authors.initials: T
authors.lastname: Uryniak
authors.forename: Steven G
authors.initials: SG
authors.lastname: Simonson
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide