Platelet-activating factor (PAF), proposed as an important inflammatory mediator in
asthma, reproduces several of the features of
asthma, such as microvascular leakage, mucus secretion, bronchoconstriction, and possibly increased airway responsiveness.
Modipafant (UK-80,067) is the (+)-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 study. A total of 218 patients with
asthma were enrolled into the single-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr) entered the double-blind treatment phase after demonstrating symptomatic
asthma in the final week of the single-blind run-in phase. Patients could take up to 1600 micrograms inhaled
corticosteroid and an inhaled beta 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
modipafant in diurnal variation in PEF, morning and evening PEF, clinic FEV1, rescue
bronchodilator usage, symptom score, or airway responsiveness. We previously showed that the racemate UK-74,505 had no effect on
antigen challenge, and this study shows that the active (+)-enantiomer
modipafant has no effect in chronic
asthma. This suggests that PAF is not an important mediator in
asthma.