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 μg (DPI‑A^*) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 μg and 180 μg; 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 μg or DPI‑A 400 μg twice-daily (total daily dose 720 μg or 800 μg), budesonide DPI‑B 180 μg or DPI‑A 200 μg once daily (total daily dose 180 μg or 200 μg), or matching placebo. Change in forced expiratory volume in 1 second (FEV₁) and secondary variables (asthma symptoms, β₂-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 μg 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 μg 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 μg versus DPI‑A 400 μg and once-daily budesonide DPI‑B 180 μg versus DPI‑A 200 μg 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 ≥ 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.

Key words: :

• Budesonide
• Drug efficacy
• Drug safety
• Dry powder inhaler
• Inhaled corticosteroids
• Pharmacokinetics