Albuterol multidose dry powder inhaler efficacy and safety versus placebo in children with asthma

Background:

A novel, inhalation-driven, multidose dry powder inhaler (MDPI) that does not require coordination of actuation with inhalation has been developed.

Objective:

To evaluate the efficacy and safety of albuterol MDPI versus placebo MDPI after chronic dosing in children with asthma.

Methods:

This phase III, double-blind, parallel-group study included children with asthma (ages, 4‐11 years) with forced expiratory volume in 1 second (FEV₁) of 50‐95% of predicted. After a 14-day run-in period wherein the patients continued their current asthma therapy and received single-blind placebo MDPI, they were randomized to albuterol MDPI 90 μg per inhalation, two inhalations four times daily (total daily dose, 720 μg), or placebo for 3 weeks. Pulmonary function was assessed on days 1 and 22. Efficacy and safety were evaluated by measuring the baseline-adjusted percent-predicted FEV₁ (PPFEV₁) area under the time curve over 6 hours (AUC_0‐6) after the dose and adverse events, respectively.

Results:

The full analysis set included 184 patients. Patients treated with albuterol MDPI versus patients treated with placebo MDPI had significantly greater baseline-adjusted PPFEV₁ AUC_0‐6 over 3 weeks (least squares mean difference, 25.0%•hour, which favored albuterol; p < 0.001). The benefit of albuterol (mean change in PPFEV₁) was evident 5 minutes after dosing and lasted several hours; the maximal effect was noted 1 to 2 hours after dosing. Albuterol MDPI was well tolerated.

Conclusions:

In children with persistent asthma, albuterol MDPI improved pulmonary function significantly better than placebo MDPI over 3 weeks of treatment. Clinical efficacy was evident within 5 minutes of dosing and maintained for >2 hours. Four times daily administration was well tolerated.