The effect of the Oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies

Investigative Ophthalmology and Visual Science

Volumn 54, Issue 3, 2013, Pages 1750-1757

  Sheetz, Matthew J ^a   Aiello, Lloyd Paul ^b   Davis, Matthew D ^c   Danis, Ronald ^c   Bek, Toke ^d   Cunha Vaz, Jose ^e   Shahri, Nazila ^f   Berg, Paul H ^a  

^a ELI LILLY AND COMPANY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^d AARHUS UNIVERSITY HOSPITAL   (Denmark)

^e UNIVERSITY OF COIMBRA   (Portugal)

^f i3 Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; RUBOXISTAURIN;

ADULT; ARTICLE; DIABETIC MACULAR EDEMA; DISEASE SEVERITY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; HUMAN; LASER COAGULATION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY (TOPIC); OPTICAL COHERENCE TOMOGRAPHY; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSPECTIVE STUDY; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETINAL THICKNESS; UNSPECIFIED SIDE EFFECT; VISUAL ACUITY; VISUAL IMPAIRMENT;

ADMINISTRATION, ORAL; DIABETIC RETINOPATHY; DOUBLE-BLIND METHOD; ENZYME INHIBITORS; FEMALE; HUMANS; INDOLES; MACULAR EDEMA; MALE; MALEIMIDES; MIDDLE AGED; PROSPECTIVE STUDIES; PROTEIN KINASE C; QUESTIONNAIRES; SICKNESS IMPACT PROFILE; TOMOGRAPHY, OPTICAL COHERENCE; VISION DISORDERS; VISUAL ACUITY;

EID: 84875430152     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.12-11055     Document Type: Article

References (18)

1. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics Fact Sheet: General Information and National Estimates on Diabetes in the United States. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health; 2005.
2. Aiello LP, Vignati L, Sheetz MJ, et al. Oral protein kinase C b inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the protein kinase C b inhibitor-diabetic retinopathy study and the protein kinase C b inhibitor-diabetic retinopathy study 2. Retina. 2011;31:2084-2094.
3. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813-820.
4. Sheetz MJ, King GL. Molecular understanding of hyperglycemia's adverse effects for diabetic complications. JAMA. 2002; 288:2579-2588.
5. Setter SM, Campbell RK, Cahoon CJ. Biochemical pathways for microvascular complications of diabetes mellitus. Ann Pharmacother. 2003;37:1858-1866.
6. Aiello LP, Bursell SE, Clermont A, et al. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes. 1997;46:1473-1480.
7. Danis RP, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKC beta inhibition with LY333531. Invest Ophthalmol Vis Sci. 1998;39:171-179.
8. Nonaka A, Kiryu J, Tsujikawa A, et al. PKC beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000; 41:2702-2706.
9. Yokota T, Ma RC, Park JY, et al. Role of protein kinase C on the expression of platelet-derived growth factor and endothelin-1 in the retina of diabetic rats and cultured retinal capillary pericytes. Diabetes. 2003;52:838-845.
10. Aiello LP, Clermont A, Arora V, et al. Inhibition of PKC beta by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest Ophthalmol Vis Sci. 2006;47:86-92.
11. The PKC-DRS Study Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter, randomized clinical trial. Diabetes. 2005;54:2188-2197.
12. The PKC-DRS2 Study Group. The effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology. 2006;113:2221-2230.
13. Girach A, Aiello LP, Milton RC, et al. Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy. Eye. 2009;23:209-214.
14. McGill JB, King GL, Berg PH, et al. Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin. Expert Opin Drug Saf. 2006;5:835-845.
15. Davis MD, Sheetz MJ, Aiello LP, et al., for the PKC-DRS2 Study Group. Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. Invest Ophthalmol Vis Sci. 2009;50:1-4.
16. PKC-DMES Study Group. Effect of ruboxistaurin in patients with diabetic macular edema. Arch Ophthalmol. 2007;125: 318-324.
17. Nicholson BP, Schachat AP. A review of clinical trials of anti-VEGF agents for diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2010;248:915-930.
18. Pelli DG, Robson JG, Wilkins AJ. The design of a new letter chart for measuring contrast sensitivity. Clin Vision Sci. 1988; 2:187-199.