Study of Rebamipide Eye Drops to Treat Dry Eye

Keratoconjunctivitis Sicca Clinical Trial

Official title:

Rebamipide Ophthalmic Suspension in the Treatment of Dry Eye: A Multicenter, Phase 3, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, 52 Week Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00201981
• Other study ID #: 37E-03-202
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: January 4, 2008
• Start date: May 2004
• Est. completion date: February 2007

Study information

• Verified date: January 2008
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the potential safety and effectiveness of rebamipide eye drops, an investigational eye drop being developed for the treatment of keratoconjunctivitis sicca (dry eye).

Description:

There is a need for effective therapy for dry eye that treats the underlying cause of the syndrome. The goal of this study is to assess the impact of rebamipide on dry eye symptom.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 740
• Est. completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• must have symptoms of dry eye for a minimum of 6 months

• must be able to sign and date an informed consent

Exclusion Criteria:

• presence of anterior segment disease

• glaucoma or ocular hypertension

• using Restasis

• use of topically instilled ocular medications during study

• use of contact lenses

• history of ocular surgery within 12 months

• females who are pregnant, breast feeding, or child-bearing potential and not willing to remain abstinent or use contraception

• presence of Stevens-Johnson syndrome

• any anticipated change in medication through-out study

• concurrent involvement in another study or previous receipt of this drug

• cannot be safely be weaned off of ocular medications

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dry Eye Syndromes
• Keratoconjunctivitis
• Keratoconjunctivitis Sicca

Intervention

Drug:
• Rebamipide
OPC as a single drop per eye (approx 50 µL) 4 times per day for 52 weeks OPC as a single drop per eye (approx 50 µL) 4 times per day for 52 weeks

Locations

Country	Name	City	State
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	St. Luke's Eye Institute	Amarillo	Texas
United States	Sall Eye Research Center	Artesia	California
United States	Omni Eye Services	Atlanta	Georgia
United States	Eye Clinic of Austin	Austin	Texas
United States	Krieger Eye Institute	Baltimore	Maryland
United States	Eye Center Northeast	Bangor	Maine
United States	Gulf Coast Research Associates, Inc.	Baton Rouge	Louisiana
United States	Alabama Research Center, LLC	Birmingham	Alabama
United States	Peter C. Donshik, MDPC	Bloomfield	Connecticut
United States	New England Eye Center	Boston	Massachusetts
United States	The Eye Associates	Bradenton	Florida
United States	Hernando Eye Institute	Brooksville	Florida
United States	Centennial Eye Associates	Centennial	Colorado
United States	Comprehensive Opthalmology & Optical Services	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Access Eye Research Center	Fredericksburg	Virginia
United States	Sun Valley Arthritis Center, Ltd.	Glendale	Arizona
United States	Danial Long, MD	Gretna	Louisiana
United States	Baylor College of Medicine	Houston	Texas
United States	Surgical Eye Associates, PA	Houston	Texas
United States	Radiant Research - Irvine	Irvine	California
United States	Scripps Clinic Medical Group, Inc.	La Jolla	California
United States	Brazosport Eye Institute	Lake Jackson	Texas
United States	Radiant Research, Inc. - Lake Worth	Lake Worth	Florida
United States	Clinical Research Center of Nevada	Las Vegas	Nevada
United States	University of Kentucky, Department of Ophthamology	Lexington	Kentucky
United States	Corneal Consultants of Colorado	Littleton	Colorado
United States	American Eye Institute	Los Angeles	California
United States	Kentucky Lions Eye Center	Louisville	Kentucky
United States	The Wilmer Eye Institute	Lutherville	Maryland
United States	University Eye Surgeons	Maryville	Tennessee
United States	Clinical Research Institute of Southern Oregon	Medford	Oregon
United States	Montana Medical Research, LLC	Missoula	Montana
United States	West Hills Vision Center	Moon Township	Pennsylvania
United States	Glaucoma Consultants and Center for Eye Research	Mt. Pleasant	South Carolina
United States	Lakeview Optical	New Orleans	Louisiana
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Mississippi Eye Associates	Ocean Springs	Mississippi
United States	Western New York Eye Center	Orchard Park	New York
United States	Eye Associates International	Ormond Beach	Florida
United States	The Eye Institute - Lahey Clinic North	Peabody	Massachusetts
United States	Pivotel Research Center	Peoria	Arizona
United States	Clinical Research Source, Inc.	Perryberg	Ohio
United States	Buena Vista Eye Care Center	Phoenix	Arizona
United States	Hope research Institute	Phoenix	Arizona
United States	Pinellas Eye Center	Pinellas Park	Florida
United States	Northwest Corneal Services	Portland	Oregon
United States	Orellana Retina Associates, PLLC	Raleigh	North Carolina
United States	Vision Surgery and Laser Center	Roseburg	Oregon
United States	Axia Research	Salt Lake City	Utah
United States	John Moran Eye Center, University of Utah	Salt Lake City	Utah
United States	Eye Clinic of San Diego	San Diego	California
United States	Physicians Research Options, LC	Sandy	Utah
United States	Radiant Research	Scottsdale	Arizona
United States	Glaucoma Consultants of the Capital Region	Slingerlands	New York
United States	Ft. Lauderdale Eye Institute	Sunrise	Florida
United States	Marvin E. Greenberg, MD PA 7	Tamarac	Florida
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	International Eye Center	Tampa	Florida
United States	Healthcare Partners Medical Group	Torrance	California
United States	Opticare Eye Health Center	Waterbury	Connecticut
United States	Western States Clinical Research, Inc.	Wheat Ridge	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (17)

Danjo Y, Watanabe H, Tisdale AS, George M, Tsumura T, Abelson MB, Gipson IK. Alteration of mucin in human conjunctival epithelia in dry eye. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2602-9. — View Citation

Davis CS, Chung Y. Randomization model methods for evaluating treatment efficacy in multicenter clinical trials. Biometrics. 1995 Sep;51(3):1163-74. — View Citation

Ferris FL 3rd, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol. 1982 Jul;94(1):91-6. — View Citation

Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient subsets. Biometrics. 1985 Jun;41(2):361-72. — View Citation

Garcher C, Bron A, Baudouin C, Bildstein L, Bara J. CA 19-9 ELISA test: a new method for studying mucus changes in tears. Br J Ophthalmol. 1998 Jan;82(1):88-90. — View Citation

Imaizumi, T, et al. Effect of OPC 12759 and cetraxate on gastric mucosal hemodynamics and oxygen sufficiency in rats-analysis by reflectance spectrophotometry. In-house Report No. 004101.

Kinoshita S, Kiorpes TC, Friend J, Thoft RA. Goblet cell density in ocular surface disease. A better indicator than tear mucin. Arch Ophthalmol. 1983 Aug;101(8):1284-7. — View Citation

Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 1995 Oct;21(4):221-32. Review. — View Citation

Nelson JD, Wright JC. Conjunctival goblet cell densities in ocular surface disease. Arch Ophthalmol. 1984 Jul;102(7):1049-51. — View Citation

Pflugfelder SC, Tseng SC, Yoshino K, Monroy D, Felix C, Reis BL. Correlation of goblet cell density and mucosal epithelial membrane mucin expression with rose bengal staining in patients with ocular irritation. Ophthalmology. 1997 Feb;104(2):223-35. — View Citation

Rivas L, Oroza MA, Perez-Esteban A, Murube-del-Castillo J. Morphological changes in ocular surface in dry eyes and other disorders by impression cytology. Graefes Arch Clin Exp Ophthalmol. 1992;230(4):329-34. — View Citation

Yamasaki K, et al. Effect of OPC 12759 on gastric mucosal blood flow in rats-determination by the hydrogen gas clearance method. In-house Report No. 003915.

Yamasaki K, et al. Effect of OPC 12759 on the production of oxygen-derived free radical from human polymorphonuclear leukocytes. In-house Report No. 004272.

Yamasaki K, Ishiyama H, Imaizumi T, Kanbe T, Yabuuchi Y. Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer, and gastric secretion in rats. Jpn J Pharmacol. 1989 Apr;49(4):441-8. — View Citation

Yamasaki K, Kanbe T, Chijiwa T, Ishiyama H, Morita S. Gastric mucosal protection by OPC-12759, a novel antiulcer compound, in the rat. Eur J Pharmacol. 1987 Oct 6;142(1):23-9. — View Citation

Yoshikawa T, Naito Y, Nakamura S, Nishimura S, Kaneko T, Iinuma S, Takahashi S, Kondo M, Yamasaki K. Effect of rebamipide on lipid peroxidation and gastric mucosal injury induced by indometacin in rats. Arzneimittelforschung. 1993 Dec;43(12):1327-30. — View Citation

Yoshikawa T, Naito Y, Tanigawa T, Kondo M. Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance. Arzneimittelforschung. 1993 Mar;43(3):363-6. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fluorescein corneal staining (FCS) total score at week 12 and the average primary ocular discomfort (POD) severity score at week 12		12 week and 26 week	No
Secondary	fluorescein corneal staining (FCS) total score at week 26 and the average primary ocular discomfort (POD) severity score at week 26		12 week and 26 week	No