Worldwide Clinical Experience With the First Marketed Leukotriene Receptor Antagonist

• Published in: Chest Vol. 111; no. 2; pp. 52S - 60S
• Main Authors: Barnes, Neil C., de Jong, Bert, Miyamoto, Terumasa
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Northbrook, IL Elsevier Inc 01.02.1997; American College of Chest Physicians
• Subjects: airway disease; allergic rhinitis; Anti-Asthmatic Agents - adverse effects; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Asthma; Biological and medical sciences; Chromones - adverse effects; Chromones - pharmacology; Chromones - therapeutic use; Clinical Trials as Topic; Dose-Response Relationship, Drug; Effectiveness; Europe; Hay fever; Humans; Japan; Leukotriene Antagonists; leukotriene receptor antagonist; Medical sciences; North America; ONO-1078; Pharmacology. Drug treatments; pranlukast; Respiratory system; Rhinitis; SB 205312; Steroids; North America; Japan; Europe; airway disease; leukotriene receptor antagonist; pranlukast; asthma; SB 205312; allergic rhinitis; ONO-1078; Human; Immunopathology; Allergy; Rhinitis; Respiratory disease; Treatment efficiency; Oral administration; Tolerance; Asthma; Leukotriene; Chemotherapy; Treatment; Pranlukast; Double blind study; Antagonist; Obstructive pulmonary disease; Biological receptor
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1378/chest.111.2_Supplement.52S

Pranlukast (SB 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 D4 (LTD4) 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 (PEFR), and a decreased need for bronchodilators and corticosteroids in the 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, 450 mg bid, to block the bronchoconstrictor effect of inhaled LTD4. A single dose of pranlukast resulted in a 10.6-fold increase in the concentration of LTD4 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 FEV1, PEFR, and asthma symptoms were noted. Ongoing studies will define further the role of pranlukast as a treatment for asthma and allergic rhinitis.