EFFECT OF A NOVEL POTENT PLATELET-ACTIVATING-FACTOR ANTAGONIST, MODIPAFANT, IN CLINICAL ASTHMA

Platelet-activating factor (PAF), proposed as an important inflammator y mediator in asthma, reproduces several of the features of asthma, su ch as microvascular leakage, mucus secretion, bronchoconstriction, and possibly increased airway responsiveness. Modipafant (UK-80,067) is t he (+)-enantiomer of UK-74,505, a potent and specific PAF antagonist. We have assessed the effect of modipafant over 28 d in adult subjects with moderately severe asthma in a placebo-controlled parallel group s tudy. A total of 218 patients with asthma were enrolled into the singl e-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr ) entered the double-blind treatment phase after demonstrating symptom atic asthma in the final week of the single-blind run-in phase. Patien ts could take up to 1600 mu g inhaled corticosteroid and an inhaled be ta(2) agonist as rescue medication. A total of 59 patients with asthma took modipafant (one 50 mg capsule twice daily), and 61 took matched placebo. There was no significant difference between placebo and modip afant in diurnal variation in PEF, morning and evening PEF, clinic FEV (1), rescue bronchodilator usage, symptom score, or airway responsiven ess. We previously showed that the racemate UK-74,505 had no effect on antigen challenge, and this study shows that the active (+)-enantiome r modipafant has no effect in chronic asthma. This suggests that PAF i s not an important mediator in asthma.