Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma

The possible roles of secretory phospholipases A(2) (sPLA(2)) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA(2)-mediated activation of cPLA(2) with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA(2). This study examined the impact of two doses of LY333013 vs. placebo on allergen-induced bronchoconstriction following inhaled allergen challenge in atopic asthmatics. Fifty subjects were randomly assigned to treatment, and 40 subjects completed the study. A double-blind, placebo-controlled, random order, crossover study design was used. LY333013 had no impact on the primary outcome variables of the areas under the FEV1 response curve early (0-3 hours) (AUC(early)) and late (3-8 hours) (AUC(late)) following inhaled allergen challenge. No significant drug-related adverse effects were observed. The response to inhaled allergen challenge was reproducible and confirms the utility of this technique as a model in which to screen compounds for further testing in asthmatic patients.