PRANLUKAST, A NOVEL LEUKOTRIENE RECEPTOR ANTAGONIST - RESULTS OF THE FIRST EUROPEAN, PLACEBO-CONTROLLED, MULTICENTER CLINICAL-STUDY IN ASTHMA

Background - Leukotriene receptor antagonists have been shown to prote ct against bronchoconstriction induced by antigens, exercise, and cold air. There are relatively few clinical studies reported in patients w ith asthma. The present study is the first clinical evaluation of pran lukast (SE 205312, ONO-1078) outside Japan in patients with asthma. Me thods - A randomised, double blind, placebo controlled, parallel group , multicentre four week study of the safety and tolerability of oral p ranlukast, 225 or 337.5 mg twice daily, was performed in patients with mild to moderate asthma. Preliminary efficacy data were obtained; the main efficacy variables evaluated were forced expiratory volume in on e second (FEV1) and morning domiciliary (home) peak expiratory flow ra tes (PEFR). Clinic PEFR and daytime and night-time asthma symptom scor es were also recorded. Results - Compared with the placebo group the i mprovement in morning home PEFR was statistically significant at all t ime points for patients receiving pranlukast 337.5 mg twice daily and at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg twice daily. Mean morning home PEFR increased by 10.8 to 18.6 l/min ( 95% CI 0.2 to 29.3 l/min) in patients treated with pranlukast compared with a slight deterioration in those given placebo. FEV1 significantl y increased within one hour after the first dose of pranlukast compare d with baseline and this increase was maintained for eight hours. Impr ovements in trough FEV1 - that is, at the end of the dosing interval - were statistically significant for the group treated with pranlukast 225 mg twice daily compared with placebo at week 4. Mean increases in FEV1 ranged from 210 ml to 340 ml (95% CI 60 to 500 ml) at trough in t he pranlukast group. Patients treated with pranlukast also showed impr ovements in summary symptom and night-time asthma scores. Pranlukast w as well tolerated, and no drug related changes in haematological and b iochemical variables were observed. Conclusions - Pranlukast, an oral leukotriene receptor antagonist, is well tolerated asthma. It increase d FEV1 within one hour of dosing, improved patient summary symptom and night-time asthma scores, and reduced the use of rescue bronchodilato rs, thus providing further evidence of a role for leukotrienes in the pathogenesis of asthma.