A Phase 2 Randomized, Double-Masked, Placebo-Controlled Study of a Novel Integrin Antagonist (SAR 1118) for the Treatment of Dry Eye

center dot PURPOSE: To investigate the efficacy and safety of an investigational integrin antagonist (SAR 1118) ophthalmic solution compared to placebo (vehicle) in subjects with dry eye disease. center dot DESIGN: Multicenter, prospective, double-masked, placebo-controlled trial. center dot METHODS: A total of 230 dry eye subjects selected with use of a controlled adverse environment were randomized 1:1:1:1 to receive SAR 1118 (0.1%, 1.0%, 5.0%) or placebo eye drops twice daily for 84 days. Principal eligibility criteria included exacerbation in corneal staining and ocular symptoms with controlled adverse environment exposure, no active lid margin disease, and Schirmer test (mm/5 min) > 1 and < 10. Ocular signs and symptoms (Ocular Surface Disease Index, OSDI) were assessed at day 14, 42, and 84. No supplemental artificial tears were allowed. Primary outcome measure was inferior corneal staining score at day 84. center dot RESULTS: A dose response for the corneal staining score (P = .0566) was observed for SAR 1118 at day 84 compared to placebo. Mean change from baseline to day 84 showed significant improvements (P < .05) in corneal staining score, total OSDI, and visual-related function OSDI scores for SAR 1118 compared to placebo; improvements in tear production and symptoms were observed as early as day 14 (P < .05). Adverse events were mild and transient in nature with no serious ocular adverse events. SAR 1118 5.0% showed increased instillation site adverse events relative to placebo but were limited to the initial dose. center dot CONCLUSION: SAR 1118 demonstrated improvements in signs and symptoms of dry eye compared to placebo and appears safe when administered over 84 days. (Am J Ophthalmol 2012;153:1050-1060. (C) 2012 by Elsevier Inc. All rights reserved.)