A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants

RATIONALE: Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States. METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma. Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients. RESULTS: Patients enrolled had an average duration of asthma of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo. CONCLUSION: Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.