A PLACEBO-CONTROLLED, DOSE-RANGING STUDY OF MONTELUKAST, A CYSTEINYL LEUKOTRIENE-RECEPTOR ANTAGONIST

Background: The cysteinyl leukotrienes are important mediators of bron chial asthma. The clinical effect of montelukast, a potent cysteinyl l eukotriene-receptor antagonist, was investigated in a randomized, plac ebo-controlled, multicenter, parallel-group, dose-ranging study. Metho ds: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled beta- agonists on at least two occasions) were randomly assigned to one of s ir treatment groups: placebo; 10, 100, or 200 mg once daily montelukas t in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout pe riod. All patients used inhaled, short-acting beta-agonists as needed. Results: All montelukast doses caused similar and significant differe nces compared with placebo in asthma control endpoints. The least-squa re mean difference between pooled montelukast groups and placebo in th e percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.5 6 to 15.04), as-needed beta-agonist use (-0.98 puffs; 95% CI: -1.53 to -0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians' and patients' global evaluations, and asthma-sp ecific quality-of-life scores were all significant (p less than or equ al to 0.050). The incidence of adverse experiences was not dose relate d and was similar between placebo and montelukast treatment. Conclusio n: Montelukast caused a significant improvement in chronic asthma at a n oral, once daily evening dose as low as 10 mg.