Inhibitory effects of BAY X 7195, a CYS leukotriene 1 receptor antagonist, on allergen-induced asthmatic responses

Background: Leukotriene antagonists may inhibit bronchoconstrictive responses to a variety of stimuli. Objective: To evaluate the efficacy and safety of a new CYS LT1 antagonist, BAY x 7195, given as a single oral dose of 500 mg, in prevention of allergen-induced asthmatic responses. Methods: This is a randomized, double-blind crossover, placebo-controlled study in mildly asthmatic non-smoking subjects (n = 10) , aged 20 to 32 years (mean 24.8). Following an initial baseline allergen challenge, the subjects came back for two other challenges separated by at least a 2-week period, during which placebo or BAY x 7195 was administered two hours before allergen inhalation. Allergen challenges were preceded and followed by a methacholine inhalation test (24 hours before and 30 hours after). Results: For each subject, the same allergen and doses were used throughout the study. In the randomized (intent-to-treat) population (n = 10), after BAY x 7195, the allergen induced % fall in FEV1 was less than after placebo, with mean between-treatment differences of 31.8 +/- 18.0% during the early asthmatic response, P = .03, and of 54.4 +/- 23.2% during the late asthmatic response (P = .04). The allergen-induced increase in methacholine responsiveness was reduced after BAY x 7195, with a change of -0.45 doubling concentrations of methacholine as compared with -1.77 after placebo; however, the change did not achieve statistical significance, P = .08. Conclusion: BAY x 7195 shows suppressive effects on allergen-induced responses, suggesting that it may be useful in the treatment of asthma.