Albuterol, Metred-Dose, Dry-Powder Inhaler Provides Effective Rescue for Children With Asthma: Presented at AAAAI

   LOS ANGELES -- March 9, 2016 -- A novel dry-powder inhaler capable of automatically delivering a pre-set dose of albuterol demonstrates effectiveness in relieving asthma symptoms in a paediatric population, according to results from a phase 3, parallel-group trial presented at the 2016 Annual Meeting of the American Allergy Asthma and Immunology (AAAAI).

The device is easy for children to use, and the automatic inhalation-triggered delivery of the dose prevents dosing errors, which are common in this age group, explained presenter Craig LaForce, MD, North Carolina Clinical Research, Raleigh, North Carolina, speaking here on March 7.

“While albuterol is currently available in multiple [metred-dose inhalers], there is an unmet need for a dry-powder inhaler rescue medication...that utilises the same delivery device for patients who use dry powder for their controller medications,” wrote Dr. LaForce and colleagues.

After a 2-week run-in period during which patients continued their current asthma therapy and received single-blind placebo using the dry-powder inhaler, Dr. LaForce and colleagues randomised 186 patients with asthma (age range: 4 to 11 years) to receive albuterol at an inhaled dose of 90 µg (n = 94, 82 subjects completed the study) or the same amount of placebo powder (n = 92, 80 subjects completed the study). The drug and placebo were delivered 4 times daily, with 2 inhalations at each time period, for a total daily dose of 720 µg. The treatment period was 3 weeks.

Participants underwent pulmonary function tests at clinic visits at the beginning of the study and again after 8 weeks. The investigators evaluated efficacy and safety by measuring the area under the baseline-adjusted percent predicted forced expiratory volume in 1 second time curve over 6 hours following delivery of the dose (PPFEV1 AUC0-6) and adverse events.

Albuterol produced significantly greater improvements in PPFEV1 AUC0-6 over the 3-week period of drug use versus placebo recipients (P < .0001). The benefit of albuterol judged by the mean change in PPFEV1 was evident at the first time point (5 minutes after dosing), and clinically meaningful bronchodilation lasted for several hours.

A total of 23% of patients in each arm experienced adverse events, most frequently headache. Four patients in the placebo group and 5 patients in the albuterol group experienced a moderately severe exacerbation of asthma. All but 1 patient receiving placebo either recovered or were recovering.

To participate in the study, subjects had to have a diagnosis of asthma at least 6 months before enrollment, with stable asthma for at least 3 weeks prior to study screening. All had used low-dose inhaled corticosteroids, leukotriene modifiers, inhaled cromones, or beta-agonists as needed for at least 4 weeks prior to the screening visit. Forced expiratory volume in 1 second (FEV1) was 50% to 95% of the predicted norm for age, height, and gender for all subjects, and all subjects had demonstrated reversible bronchoconstriction; the ability to use a handheld metre to record peak expiratory flow (PEV); and the ability to use the dry-powder inhaler.

The investigators excluded individuals who had sensitivity to albuterol or any components of the dry-powder formulation, a respiratory-tract infection/disorder within 4 weeks of screening, or an asthma exacerbation requiring corticosteroid treatment within 6 months of screening.

Baseline demographic and clinical characteristics were similar in both study arms.

“Albuterol metred-dose dry-powder inhaler, administered chronically for 3 weeks, improved pulmonary function in paediatric patients significantly better than placebo,” Dr. LaForce concluded, adding that clinical effects were evident within 5 minutes after dosing and were maintained for ≥2 hours. Four-times-daily administration was generally well tolerated in this paediatric population.
Funding for this study was provided by Teva Pharmaceutical, Cambridge, Massachusetts.

[Presentation title: Efficacy and Safety of Albuterol Multidose Dry Powder Inhaler (MDPI) Versus Placebo in Children With Asthma. Abstract P681]