Subject(s)
Azepines/therapeutic use , Orexin Receptor Antagonists/therapeutic use , Sleep Aids, Pharmaceutical/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Triazoles/therapeutic use , Animals , Azepines/adverse effects , Azepines/chemistry , Azepines/pharmacology , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Orexin Receptor Antagonists/adverse effects , Orexin Receptor Antagonists/chemistry , Orexin Receptor Antagonists/pharmacology , Sleep Aids, Pharmaceutical/adverse effects , Sleep Aids, Pharmaceutical/chemistry , Sleep Aids, Pharmaceutical/pharmacology , Sleep Initiation and Maintenance Disorders/physiopathology , Triazoles/adverse effects , Triazoles/chemistry , Triazoles/pharmacologyABSTRACT
OBJECTIVES: In Japan, the Asthma Prevention and Management Guidelines recommend nebulized ß-agonists, IV (intravenous) drip corticosteroids, as well as IV drip aminophylline for acute asthma treatment. However, current treatment for acute asthma provides inadequate benefit for some patients. We evaluated the efficacy and safety of IV montelukast added to standard therapy in Japanese patients with acute asthma exacerbations. METHODS: This multicenter, randomized, double-blind, parallel-group study compared IV montelukast 7 mg, 14 mg, and placebo in Japanese patients with acute asthma exacerbations (N = 242). Fifteen- to sixty-five-year-old patients with acute asthma were treated with standard care during a screening period that lasted ≤60 minutes. Patients with FEV(1) (forced expiratory volume in 1 second) ≤70 predicted were randomly allocated to one of three treatment groups. The primary end point was the time-weighted average change in FEV(1) from baseline over 60 minutes [ΔFEV(1) (0-60 minutes)] after study drug administration. Secondary end points included the time-weighted average change in FEV(1) over 20, 40, and 120 minutes [ΔFEV(1) (0-T min)]. RESULTS: IV montelukast 7 mg was significantly more effective than placebo for the time-weighted average ΔFEV(1) (0-60 minutes) [least squares (LS) mean 0.09 L vs. 0.01 L; p < .05]. IV montelukast 14 mg was also more effective than placebo (LS mean 0.17 L; p < .001). Similar improvements in time-weighted average [ΔFEV(1) (0-T min)] were seen at all time points (all p < .05). Both doses of IV montelukast demonstrated a significant increase in average ΔFEV(1) compared with placebo within 10 minutes of administration (p < .001 to p < .01). The tolerability of IV montelukast was similar to that of placebo. CONCLUSION: IV montelukast was significantly more effective than placebo in the improvement of ΔFEV(1) in Japanese patients, suggesting its role as an adjunctive therapy to existing guideline recommendations.
