title: Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study.
abstract: OBJECTIVE
  To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye.
  
  
  METHODS
  A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study.
  
  
  METHODS
  A total of 308 patients with dry eye.
  
  
  METHODS
  After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks.
  
  
  METHODS
  The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score.
  
  
  RESULTS
  Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups.
  
  
  CONCLUSIONS
  Rebamipide was effective in treating both objective signs and subjective symptoms of dry eye and were well tolerated in this 4-week study. Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide in some measures.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. shigeruk@koto.kpu-m.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Saki
authors.initials: S
authors.lastname: Awamura
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Oshiden
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nakamichi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000975:Antioxidants / Q000008:administration & dosage*; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D019793:Fluorescein; D015590:Fluorophotometry; D006801:Humans; D008086:Lissamine Green Dyes; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D015363:Quinolones / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D008086:Lissamine Green Dyes; D009883:Ophthalmic Solutions; D015363:Quinolones; C024537:green 5; C052785:rebamipide; D000409:Alanine; D019793:Fluorescein