Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis

Background: Epinastine hydrochloride is a nonsedating antihistamine with a high affinity for histamine H-1 receptors, together with mast cell-stabilizing and anti-inflammatory activities. Objective: The aim of this study was to assess the efficacy and tolerability of topically administered ophthalmic epinastine using the conjunctival antigen challenge (CAC) model in patients with a history of allergic conjunctivitis. Methods: This prospective, single-center, randomized, double-masked, vehicle-controlled, Phase III clinical trial was conducted at the Ophthalmic Research Associates study center (North Andover, Massachusetts) from November 2000 to January 2001. Eligible participants were asymptomatic but had a history of allergic conjunctivitis and had positive CAC reactions at the initial screening (week 0) and at a confirmation visit (week 1). Patients were randomly assigned by eye to receive epinastine hydrochloride 0.05% ophthalmic solution in 1 eye and vehicle in the contralateral eye. Each eye received 1 drop of study medication 15 minutes before antigen application (onset challenge; week 3) or 8 hours before antigen application (duration challenge; week 5). Primary end points were ocular itching and conjunctival hyperemia. Itching was recorded 3, 5, and 10 minutes after antigen challenge. Hyperemia was recorded 5, 10, and 20 minutes after antigen challenge, as were secondary end points, which included eyelid swelling, episcleral and ciliary hyperemia, chemosis, tearing, and ocular mucous discharge. Tolerability was assessed by patient interview and slit-lamp biomicroscopy. Results: Sixty-seven patients (37 females, 30 males; mean [SD] age, 38.4 [14.2] years [range, 12-67 years]) were included in the study. Mean severity scores for the following signs and-symptoms were significantly lower with epinastine compared with vehicle at all time points after onset and duration challenges: ocular itching (P < 0.001); eyelid swelling (P < 0.001); conjunctival (P < 0.001), episcleral (P < 0.001), and ciliary hyperemia (P < 0.001); and chemosis (P <= 0.009). The percentage of eyes with tearing was significantly lower with epinastine compared with vehicle at all time points (P <= 0.021), except at 5 minutes after the duration challenge. Adverse events (AEs), reported for 7.5% (5/67) of patients, included only symptoms of upper respiratory tract infection. No ocular or treatment-related AEs were reported. Conclusions: In this CAC model, multiple signs and symptoms of allergic conjunctivitis were significantly reduced by instillation of epinastine compared with vehicle. Epinastine showed prompt onset (3 minutes) and long duration of action (>= 8 hours). The tolerability of epinastine was similar to that of vehicle. Copyright (C) 2004 Excerpta Medica, Inc.