Worldwide clinical experience with the first marketed leukotriene receptor antagonist

Pranlukast (SE 205312, ONO-1078) is an orally active, potent, selective blocker of peptidyl-leukotriene receptors. Pranlukast has been studied in a worldwide clinical development program and recently was approved in Japan for the treatment of asthma, This worldwide experience includes a pivotal safety and efficacy study conducted in Japan, a leukotriene D-4 (LTD(4)) challenge study conducted in Europe, and two safety, tolerability, and clinical activity studies conducted in Europe and North America. The pivotal study was a randomized, double-blind, 8-week comparison of pranlukast. 225 mg bid, and azelastine, 2 mg bid, Improvements in asthma symptom scores, morning and evening peak expiratory flow rate (PEER), and a decreased need for bronchodilators and corticosteroids in die pranlukast-treated group were statistically significant when compared with those in the azelastine-treated group, The most common adverse experiences were GI, The European challenge study evaluated the ability of 5-day therapy with pranlukast, 150 mg bid, to block the bronchoconstrictor effect of inhaled LTD(4). A single dose of pranlukast resulted in a 10.6-fold increase in the concentration of LTD(4) required to produce a 35% decrease in specific airways conduction; following 5 days of therapy, this increased to 25.9-fold. The two safety, tolerability, and clinical activity studies were randomized, double-blind, placebo-controlled, 4-week evaluations of pranlukast, 225 to 450 mg bid, Improvements in FEV(1), PEFR, and asthma symptoms were noted, Ongoing studies will define further the role of pranlukast as a treatment for asthma and allergic rhinitis.