title: A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  SAR 1118 demonstrated improvements in signs and symptoms of dry eye compared to placebo and appears safe when administered over 84 days.
authors.affiliation: SARcode Bioscience, Brisbane, CA 94005, USA. cpsemba@sarcode.com
authors.forename: Charles P
authors.initials: CP
authors.lastname: Semba
authors.forename: Gail L
authors.initials: GL
authors.lastname: Torkildsen
authors.forename: John D
authors.initials: JD
authors.lastname: Lonsdale
authors.forename: Eugene B
authors.initials: EB
authors.lastname: McLaurin
authors.forename: Joel A
authors.initials: JA
authors.lastname: Geffin
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Mundorf
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Kennedy
authors.forename: George W
authors.initials: GW
authors.lastname: Ousler
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D013666:Tears / Q000737:chemistry / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D009883:Ophthalmic Solutions