Time to Onset and Duration of Action of the Antihistamine Bepotastine Besilate Ophthalmic Solutions 1.0% and 1.5% in Allergic Conjunctivitis: A Phase III, Single-Center, Prospective, Randomized, Double-Masked, Placebo-Controlled, Conjunctival Allergen Challenge Assessment in Adults and Children

Background: Bepotastine besilate is a highly selective histamine Hi-receptor antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory activity. Based on a history of clinical effectiveness and tolerability of oral bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate is being tested as a potential ophthalmic medication for allergic conjunctivitis. Objective: The aim of this study was to assess the effects of bepotastine besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in adults and children. Methods: This Phase III, single-center, prospective, randomized, double-masked, placebo-controlled, CAC clinical trial enrolled patients >= 10 years of age with a history of allergic conjunctivitts, skin-test reaction, and CAC response. Patients received bepotastine besilate ophthalmic solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, I drop on each eye on days 14 +/- 3 and 28 +/- 3. The primary efficacy end points, patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator-assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical significance was defined in the protocol as >= 1.0-U between-group difference in mean ocular itching scores at the majority of time points at a study visit and also a >= 0.5-U difference at all time points. Tolerability of the test agent was assessed by visual acuity, slit-lamp biomicroscopy, Intraocular pressure, dilated funduscopy, and adverse events. Results: A total of 107 patients (male, 54%; age range, 11-73 years; white race/ethnicity, 93%) received investigational product and comprised the intent-to-treat (ITT) population (bepotastine besilate ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution 1.5%, 35; and placebo, 36). All 107 patients received investigational product at visit 3A (day 0) and were included in the ITT population. Of the 107 patients who were enrolled, 103 completed the study without a protocol deviation or violation. The 1.0% and 1.5% solutions were associated with clinically and statistically significant reductions in mean ocular itching scores compared with placebo on the 15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions, 1.3-1.5 U and 1.0-1.7 U respectively; all, P < 0.001). Statistical-ly significant reductions in conjunctival hyperemia were achieved with both bepotastine besilate concentrations. Overall, 3 patients experienced a treatment-emergent adverse event considered related to the study drug (bepotastine besilate ophthalmic solution 1.0%), 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and placebo, 3). Conclusions: In this CAC model of allergic conjunctivitis in adults and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were associated with clinically and statistically significant reductions in ocular itching, but not conjunctival hyperemia, within 1.5 minutes that were maintained for at least 8 hours after administration. Both solutions were well tolerated. ClinicalTrials.gov identifier: NCT00424398 (Clin Ther. 2009;31:1.908-1921) (C) 2009 Excerpta Medica Inc.