A phase I randomized, placebo-controlled, dose-exploration study of single-dose inhaled montelukast in patients with chronic asthma.

ABSTRACT

BACKGROUND: The efficacy of oral montelukast has been well established in asthma and allergic rhinitis in adults and children. The purpose of this study was to evaluate dose-related bronchodilation and tolerability of inhaled montelukast. METHODS: Randomized, double-blind, crossover, adaptive-design study comparing single-dose administration of inhaled montelukast versus placebo in patients age 15-65 years with chronic asthma (n = 68). Montelukast was delivered as a witnessed dose through dry powder inhaler at doses of 25, 250, or 1000 µg, and doses of 50, 100, and 500 µg could be used if needed based on a prespecified dose-response algorithm. Each administration was followed by a 4- to 7-day washout period before crossing over to the next treatment. The primary endpoint was the change from baseline in a forced expiratory volume in 1 second (FEV1) over the first 4 hours after administration, calculated as a time-weighted average (ΔFEV1 [0-4 hours]). Other endpoints included the onset and duration of bronchodilation and the effect of albuterol when added to inhaled montelukast. RESULTS: Over 4 hours postdose, and compared with placebo (least-squares [LS] mean 0.03 L), inhaled montelukast 100 µg (0.13 L; p ≤ .001), 250 µg (0.10 L; p < .01), and 1000 µg (0.12 L; p ≤ .001) had significantly greater ΔFEV1 (0-4 hours). At 24 hours postdose, inhaled montelukast 100 µg (0.10 L) and 1000 µg (0.09 L) had significantly greater bronchodilation compared with placebo (0.02 L; p < .05 vs. montelukast). Montelukast 1000 µg provided significant bronchodilation versus placebo within 20 minutes of administration (0.03 L vs. -0.05 L), whereas montelukast 100 µg provided significant bronchodilation relative to placebo within 2 hours of dosing (0.09 L vs. 0.01 L). Montelukast (pooled doses) plus albuterol was significantly more effective than montelukast plus placebo for ΔFEV1 (0-90 minutes) (0.34 L vs. 0.15 L; p = .015). The tolerability of inhaled montelukast was similar to that of placebo. No serious adverse experiences were reported. CONCLUSIONS: Inhaled montelukast provided significant bronchodilation compared with placebo as early as 20 minutes after the administration that persisted for 24 hours and provided additive bronchodilation to albuterol.