Literature DB >> 22330307

A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye.

Charles P Semba1, Gail L Torkildsen, John D Lonsdale, Eugene B McLaurin, Joel A Geffin, Thomas K Mundorf, Kathryn S Kennedy, George W Ousler.   

Abstract

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.
DESIGN: Multicenter, prospective, double-masked, placebo-controlled trial.
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.
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.
CONCLUSION: SAR 1118 demonstrated improvements in signs and symptoms of dry eye compared to placebo and appears safe when administered over 84 days.
Copyright © 2012 Elsevier Inc. All rights reserved.

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Year:  2012        PMID: 22330307     DOI: 10.1016/j.ajo.2011.11.003

Source DB:  PubMed          Journal:  Am J Ophthalmol        ISSN: 0002-9394            Impact factor:   5.258


  34 in total

1.  Factors predicting the ocular surface response to desiccating environmental stress.

Authors:  Anastasia Alex; Austin Edwards; J Daniel Hays; Michelle Kerkstra; Amanda Shih; Cintia S de Paiva; Stephen C Pflugfelder
Journal:  Invest Ophthalmol Vis Sci       Date:  2013-05-07       Impact factor: 4.799

Review 2.  [Novel current and future therapy options for treatment of dry eye disease].

Authors:  E M Messmer
Journal:  Ophthalmologe       Date:  2018-02       Impact factor: 1.059

3.  Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye.

Authors:  Min Zhong; Thomas R Gadek; Minna Bui; Wang Shen; John Burnier; Kenneth J Barr; Emily J Hanan; Johan D Oslob; Chul H Yu; Jiang Zhu; Michelle R Arkin; Marc J Evanchik; W Mike Flanagan; Ute Hoch; Jennifer Hyde; Saileta Prabhu; Jeffrey A Silverman; Jasmin Wright
Journal:  ACS Med Chem Lett       Date:  2012-01-31       Impact factor: 4.345

Review 4.  Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease.

Authors:  Gillian M Keating
Journal:  Drugs       Date:  2017-02       Impact factor: 9.546

5.  Development of sustained-release microspheres for the delivery of SAR 1118, an LFA-1 antagonist intended for the treatment of vascular complications of the eye.

Authors:  Sarath Yandrapu; Uday B Kompella
Journal:  J Ocul Pharmacol Ther       Date:  2012-12-20       Impact factor: 2.671

6.  Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118).

Authors:  Yan Sun; Rui Zhang; Thomas R Gadek; Charles A O'Neill; Eric Pearlman
Journal:  J Ocul Pharmacol Ther       Date:  2012-12-05       Impact factor: 2.671

7.  Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye.

Authors:  Karen Meerovitch; Gail Torkildsen; John Lonsdale; Heidi Goldfarb; Teresa Lama; Garth Cumberlidge; George W Ousler
Journal:  Clin Ophthalmol       Date:  2013-06-26

8.  Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy.

Authors:  Paulo J Gomes; George W Ousler; Donna L Welch; Lisa M Smith; Jeffrey Coderre; Mark B Abelson
Journal:  Clin Ophthalmol       Date:  2013-01-20

9.  A single-center study evaluating the effect of the controlled adverse environment (CAE(SM)) model on tear film stability.

Authors:  Richard Abelson; Keith J Lane; John Rodriguez; Patrick Johnston; Endri Angjeli; George Ousler; Douglas Montgomery
Journal:  Clin Ophthalmol       Date:  2012-11-13

Review 10.  Dry eye as a mucosal autoimmune disease.

Authors:  Michael E Stern; Chris S Schaumburg; Stephen C Pflugfelder
Journal:  Int Rev Immunol       Date:  2013-02       Impact factor: 5.311

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