EFFECTS OF 6 WEEKS OF THERAPY WITH ORAL DOSES OF ICI-204,219, A LEUKOTRIENE D-4 RECEPTOR ANTAGONIST, IN SUBJECTS WITH BRONCHIAL-ASTHMA

The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leu kotriene D-4 (LTD(4)) receptor antagonist, was evaluated in subjects w ith moderate asthma during a multicenter, double-blind, randomized, pl acebo-controlled, dose-ranging study. Subjects who entered the trial h ad been chronically treated for asthma with beta agonist alone or in c ombination with theophylline. Subjects were randomized to treatment wi th twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if th ey had an FEV(1) between 40 and 75% of predicted values without bronch odilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk ) for 7 consecutive d. Efficacy was evaluated from the results of symp tom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diar y card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy criteria without increasing th e number or severity of adverse events. The 40 mg dose was more effect ive than placebo (p < 0.05) in reducing nighttime awakenings, first mo rning asthma symptoms, the daytime asthma score, and albuterol use and in increasing evening peak expiratory flow (PEF) rates as well as FEV (1). Compared with baseline measurements, the 40 mg dose decreased awa kenings by 46%, albuterol use by 30%, and daytime symptoms by 26% and increased FEV(1) by 11%. ICI 204,219 improves objective and subjective measures of asthma severity in moderately ill asthmatic subjects and may provide a new treatment option for the disease.