Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

Abstract

Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma.

Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥ 12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN).

Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤ 1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis.

Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma.

Trial registration: ClinicalTrials.gov NCT01424813 NCT01698320 NCT01747629.

Keywords: Albuterol; asthma; dry powder inhaler; inhalation device; safety.

Figure 1.

Study design of three pivotal phase three studies (ABS-AS-301, ABS-AS-304 and ABS-AS-307). HFA, hydrofluoroalkane; MDI, metered-dose inhaler; MDPI, multidose dry powder inhaler; PRN, as needed; QID, four times a day. ^aAll patients were provided with an albuterol HFA MDI to use as needed for breakthrough asthma symptoms. ^bFinal follow-up of adverse events was conducted 3 (±1) days after the last treatment visit.

Figure 2.

Patient disposition for the integrated safety population. MDPI, multidose dry powder inhaler; QID, four times a day. ^aOne patient in one of the 12-week double-blind studies took both albuterol MDPI and placebo MDPI in error and was therefore included in both treatment groups of the safety population. Thus, 321 patients were treated with albuterol MDPI 180 µg QID and 333 patients were treated with placebo MDPI.