The Effect of Ruboxistaurin on Visual Loss in Patients With Moderately Severe to Very Severe Nonproliferative Diabetic Retinopathy
- 1 July 2005
- journal article
- clinical trial
- Published by American Diabetes Association in Diabetes
- Vol. 54 (7), 2188-2197
- https://doi.org/10.2337/diabetes.54.7.2188
Abstract
The purpose of this study was to evaluate the Safety and efficacy of the orally administered protein kinase C (PKC) β isoform-selective inhibitor ruboxistaurin (RBX) in subjects with moderately severe to very severe nonproliferative diabetic retinopathy (NPDR). In this multicenter, double-masked, randomized, placebo-controlled study, 252 subjects received placebo or RBX (8, 16, or 32 mg/day) for 36–46 months. Patients had an Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy severity level between 47B and 53E inclusive, an ETDRS visual acuity of 20/125 or better, and no history of scatter (panretinal) photocoagulation. Efficacy measures included progression of DR, moderate visual loss (MVL) (doubling of the visual angle), and sustained MVL (SMVL). RBX was well tolerated without significant adverse effects but had no significant effect on the progression of DR. Compared with placebo, 32 mg/day RBX was associated with a delayed occurrence of MVL (log rank, P = 0.038) and of SMVL (P = 0.226). RBX reduction of SMVL was evident only in eyes with definite diabetic macular edema at baseline (10% 32 mg/day RBX vs. 25% placebo, P = 0.017). In multivariable Cox proportional hazard analysis, 32 mg/day RBX significantly reduced the risk of MVL compared with placebo (hazard ratio 0.37 [95% CI 0.17–0.80], P = 0.012). In this clinical trial, RBX was well tolerated and reduced the risk of visual loss but did not prevent DR progression.Keywords
This publication has 43 references indexed in Scilit:
- Quality of life associated with visual loss: A time tradeoff utility analysis comparison with medical health statesOphthalmology, 2003
- Inhibition of protein kinase C decreases prostaglandin‐induced breakdown of the blood‐retinal barrierJournal of Cellular Physiology, 2003
- Role of vascular endothelial growth factor in diabetic vascular complicationsKidney International, 2000
- Blockade of Vascular Endothelial Cell Growth Factor Receptor Signaling Is Sufficient to Completely Prevent Retinal NeovascularizationThe American Journal of Pathology, 2000
- VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cellsOncogene, 1999
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)The Lancet, 1998
- Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research GroupDiabetes, 1997
- Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth.JCI Insight, 1996
- Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β InhibitorScience, 1996
- (S)-13-[(Dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno- 1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione (LY333531) and Related Analogues: Isozyme Selective Inhibitors of Protein Kinase CβJournal of Medicinal Chemistry, 1996