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

American Journal of Ophthalmology

Volumn 153, Issue 6, 2012, Pages 1050-1060.e1

  Semba, Charles P ^a   Torkildsen, Gail L ^b   Lonsdale, John D ^d   McLaurin, Eugene B ^e   Geffin, Joel A ^f   Mundorf, Thomas K ^g   Kennedy, Kathryn S ^h   Ousler, George W ^c  

^a SARcode Bioscience   (United States)

^b Andover Eye Associates   (United States)

^c Ora Inc   (United States)

^d Central Maine Eye Care   (United States)

^e Total Eye Care PA   (United States)

^f The Eye Care Group   (United States)

^g Mundorf Eye Center   (United States)

^h Statistics and Data Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS ACTING ON THE EYE; PLACEBO; SAR 1118; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DRY EYE; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL;

EID: 84861184389     PISSN: 00029394     EISSN: 18791891     Source Type: Journal    
DOI: 10.1016/j.ajo.2011.11.003     Document Type: Article

References (33)

1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007) Ocul Surf 5 2 2007 75 92
2. S.E. Moss, R. Klein, B.E. Klein Prevalence of and risk factors for dry eye syndrome Arch Ophthalmol 118 9 2000 1264 1268
3. B. Miljanovic, R. Dana, D.A. Sullivan, D.A. Schaumberg Impact of dry eye syndrome on vision-related quality of life Am J Ophthalmol 143 3 2007 409 415
4. N.J. Friedman Impact of dry eye disease and treatment on quality of life Curr Opin Ophthalmol 21 4 2010 310 316
5. M.E. Stern, S.C. Pflugfelder Inflammation in dry eye Ocul Surf 2 2 2004 124 130
6. M. Calonge, A. Enriquez-de-Salamanca, Y. Diebold Dry eye disease as an inflammatory disorder Ocul Immunol Inflamm 18 4 2010 244 253
7. J. Gao, G. Morgan, D. Tieu ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögren's syndrome-like MRL/lpr mice Exp Eye Res 78 4 2004 823 835
8. J. Gao, T.A. Schwalb, J.V. Addeo, C.R. Ghosn, M.E. Stern The role of apoptosis in the pathogenesis of canine keratoconjunctivitis sicca: the effect of topical cyclosporin A therapy Cornea 17 6 1998 654 663
9. M.E. Stern, J. Gao, T.A. Schwalb Conjunctival T-cell populations in Sjögren's and non-Sjögren's patients with dry eye Invest Ophthalmol Vis Sci 43 8 2002 2609 2614
10. H. Lam, L. Bleiden, C.S. De Paiva, W. Farley, M.E. Stern, S.C. Pflugfelder Tear cytokine profiles in dysfunctional tear syndrome Am J Ophthamol 147 2 2009 198 205
11. A. Smith, P. Stanley, K. Jones, L. Svensson, A. McDowell, N. Hogg The role of the integrin LFA-1 in T-lymphocyte migration Immunol Rev 218 2007 135 146
12. N.C. Hartman, J.A. Nye, J.T. Groves Cluster size regulates protein sorting in the immunological synapse Proc Natl Acad Sci U S A 106 31 2009 12729 12734
13. K. Miyamoto, S. Khosrof, S.E. Bursell Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition Proc Natl Acad Sci U S A 96 19 1999 10836 10841
14. S.M. Whitcup, N. Hikita, M. Shirao Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis Exp Eye Res 60 6 1995 597 601
15. T.R. Gadek, D.J. Burdick, R.S. McDowell Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule Science 295 5557 2002 1086 1089
16. S.M. Keating, K.R. Clark, L.D. Stefanich Competition between intercellular adhesion molecule-1 and a small-molecule antagonist for a common binding site on the alpha1 subunit of lymphocyte function-associated antigen-1 Protein Sci 15 2 2006 290 303
17. C.J. Murphy, E. Bentley, P.E. Miller The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs Invest Ophthalmol Vis Sci 52 6 2011 3174 3180
18. V.R. Rao, E. Prescott, N.B. Shelke Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR) Invest Ophthalmol Vis Sci 51 10 2010 5198 5204
19. C.P. Semba, D. Swearingen, V.L. Smith Safety and pharmacokinetics of a novel lymphocyte function-associated antigen-1 antagonist ophthalmic solution (SAR 1118) in healthy adults J Ocul Pharmcol Ther 27 1 2011 99 104
20. Restasis® (cyclosporine ophthalmic emulsion) 0.05% Full Prescribing Information http://www.allergan.com/assets/pdf/restasis-pi.pdf Accessed: June 30, 2011
21. J.D. Sheppard, S.V. Scoper, S. Samudre Topical loteprednol pretreatment reduces cyclosporine stinging in chronic dry eye disease J Ocul Pharmacol Ther 27 1 2011 23 27
22. G.W. Ousler, P.J. Gomes, D. Welch, M.B. Abelson Methodologies for the study of ocular surface disease Ocul Surf 3 3 2005 143 154
23. R.M. Schiffman, M.D. Christianson, G. Jacobsen, J.D. Hirsch, B.L. Reis Reliability and validity of the Ocular Surface Disease Index Arch Ophthalmol 118 5 2000 615 621
24. International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Medical Dictionary for Regulatory Activities Maintenance and Support Services Organization http://www.meddramsso.com Accessed December 1, 2011.
25. M.A. Patane, A. Cohen, S. From, G. Torkildsen, D. Welch, G.W. Ousler Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial Clin Ophthalmol 5 2011 633 643
26. M.T. Christensen Corneal staining reductions observed after treatment with Systane Lubricant Eye Drops Adv Ther 25 11 2008 1191 1199
27. K. Sall, O.D. Stevenson, T.K. Mundorf, B.L. Reis CsA Phase 3 Study Group Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease Ophthalmology 107 4 2000 631 639
28. J. Tauber, W.F. Davitt, J.E. Bokosky Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for treatment of dry eye Cornea 23 8 2004 784 792
29. K.L. Miller, J.G. Walt, D.R. Mink Minimal clinically important difference for the Ocular Surface Disease Index Arch Ophthalmol 128 1 2010 94 101
30. R. Vogel, S. Crockett, N. Oden, T.W. Laliberte, L. Molina Sodium Hyaluronate Ophthalmic Solution Study Group Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (Vismed, Rejena) Am J Ophthalmol 149 4 2010 594 601
31. New Drug Application (NDA) 21-023 Medical Review. Center for Drug Evaluation and Research, US Food and Drug Administration http://www.accessdata. fda.gov/drugsatfda-docs/nda/2003/21-023-Restasis-Medr.PDF Accessed: June 30, 2011
32. K.K. Nichols, J.J. Nichols, G.L. Mitchell The lack of association between signs and symptoms in patients with dry eye disease Cornea 23 8 2004 762 770
33. Design and conduct of clinical trials report of the Clinical Trials Subcommittee of the International Dry Eye Workshop (2007) Ocul Surf 5 2 2007 153 162