The conjunctival provocation test model of ocular allergy: Utility for assessment of an ocular corticosteroid, loteprednol etabonate

Two studies were conducted using the conjunctival provocation test (CPT) mo del of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was lot eprednol etabonate 0.5%, previously found effective in the treatment of ocu lar allergy and inflammation. The study was a randomized double-masked, pla cebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i. d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic respo nse received LE in one eye and placebo in the fellow eye for 28 days from D ay 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline) , 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vesse l beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statisticall y significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the sele ction of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized doub le-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0 .1%, 0.2% and 0.3%, q.i.d in 88 subjects. The dosing and testing regimen wa s similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0 .2% and 0.3%, was numerically superior to the placebo in reducing mean redn ess and itching. At the 20-minute post allergen challenge, the 0.1% concent ration was significantly superior (p < 0.05) to the placebo on Visit 4 (2 a nd 4 hour challenge) in reducing the mean redness; however, LE was only num erically superior in relieving itching. The 0.2% concentration was signific antly superior (p < 0.05) to the placebo in the reduction of mean redness a nd itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness on all visits, and st atistically significant in the reduction of itching on Visit 4 (4 hour chal lenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this m odel, 0.2% loteprednol etabonate was selected for further evaluation in env ironmental seasonal allergic conjunctivitis studies.