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New Medical Therapies™

Diabetic Retinopathy

September 22, 2008

AstraZeneca issued mixed results from three phase III trials of candesartan for the treatment of diabetic retinopathy. These international, double blind, randomized, placebo controlled studies were part of a program called DIRECT, comprised of: DIRECT-Prevent 1, which studied the effect of candesartan on the incidence of retinopathy (primary endpoint) in 1,421 normotensive, normoalbuminuric Type I diabetic subjects; DIRECT-Protect 1, which studied the effect of candesartan on the progression of retinopathy (primary endpoint) in 1,905 normotensive, normoalbuminuric Type I diabetic subjects already affected by retinopathy and DIRECT-Protect 2, which studied the effect of candesartan on the progression of retinopathy (primary endpoint) in 1.905 normoalbuminuric, normotensive or treated hypertensive, Type II diabetic subjects with retinopathy. The subjects in the active treatment group received a 32mg dose of candesartan for between four and six years. The primary endpoints were not reached. While the data showed a trend in favor of treatment with candesartan in reducing the incidence of diabetic retinopathy, the results were not statistically significant. However, in the population of Type I diabetics with no signs of diabetic retinopathy at baseline, candesartan caused an 18% reduction in the incidence of diabetic retinopathy as measured by 2-step change on the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale (p=0.0508) and a 35% reduction for 3-step change (post-hoc analysis, p=0.003). Treatment with candesartan also reduced the risk of progression of retinopathy by 13% over placebo in Type II diabetics (p=0.2). In the population of Type II diabetics with relatively early signs of diabetic retinopathy, candesartan increased the probability of regression of retinopathy by 34% compared with placebo, a pre-defined secondary endpoint (p=0.009). In Type 1 diabetic subjects with retinopathy at baseline there were no differences in the results in progression of retinopathy between the two treatment groups (p=0.85). Based on the data, AstraZeneca plans to continue with the development of candesartan for this indication.

September 25, 2006

SurModics issued positive results from a phase I trial of I-vation, an intravitreal implant designed to deliver drugs on a sustained-release basis, for the treatment of Diabetic Macular Edema (DME). This trial, dubbed STRIDE (Sustained Triamcinolone Release for Inhibition of Diabetic Macular Edema) enrolled 30 subjects at four sites in the US, who received the implant and were observed for six months. Safety profiles revealed treatment to be well tolerated with no serious adverse events reported and no sustained elevation of intraocular pressure. Efficacy results were positive as well with 100% of the subjects either maintaining or improving vision, as measured by the ETDRS eye chart. Based on the data, SurModics plans to move development of I-vation forward.

November 1, 2004

GenVec reported positive results of a phase I trial of AdPEDF in patients with wet age-related macular degeneration (AMD) at the Subspecialty Retina Day symposium of the first joint session of the American Academy of Ophthalmology and the European Ophthalmology Society. Trial data met the primary safety and tolerability endpoints, with no dose-limiting toxicities, serious adverse events, or treatment-related infections. Secondary evidence of efficacy was also noted, with observed improvements in appearance of retinal health and stabilization of visual acuity. This open-label, dose escalating study enrolled 28 AMD patients into one of 8 dosing cohorts across six US sites. GenVec announced plans to investigate the drug in patients with less severe AMD to investigate efficacy.

ISTA Pharmaceuticals presented combined the results of a pair of phase III trials of Xibrom (bromefac sodium ophthalmic solution), for the treatment of ocular inflammation, eye pain and photosensitivity following cataract surgery. The combined data from the two trials (both conducted under the same protocol) indicated that a significantly larger portion of patients treated with Xibrom met the primary efficacy endpoint compared with placebo, as measured by the incidence of patients with complete absence of ocular inflammation at the end of the dosing period (64% vs. 40%; p<0.0001). Additional evidence of rapid, three day efficacy was also observed, and the Xibrom group experienced a lower incidence of adverse events than the placebo group. The randomized, double-blind, placebo-controlled studies enrolled a total of 527 subjects across 39 US sites, who received either topical Xibrom or placebo twice daily for 14 days, following surgical cataract removal.

Lilly has issued the results of a pair of analyses of two phase III trials of their investigational compound ruboxistaurin, for the treatment of diabetic macular edema (DME). Combined trial data indicated that the drug was efficacious in treating DME, promoting better visual acuity compared with subjects with similar degrees of macular damage receiving placebo, as measured by the number of correctly identified letters (71 vs. 60, p<0.01). In addition, a trend towards reduced DME progression was observed in subjects with significant degeneration near but not directly involving the macula, compared with placebo (20% vs. 31%, p=0.083). Both phase III trials were double-blind, long term investigations (30 and 36 month minimum durations), and enrolled more than 900 patients with DME. Lilly announced that these analyses would be used to support an ongoing phase III trial of the drug.

January 14, 2002

Positive results were reported from a randomized, placebo-controlled pilot phase IIa trial of Vitrase, Ista Pharmaceuticals' potential treatment for diabetic retinopathy. The progression of diabetic retinopathy was assessed by reviewing fundus photographs to determine an ETDRS (Early Treatment for Diabetic Retinopathy Study) retinopathy severity scale score for each subject's study eye. These ETDRS retinopathy severity scores were then evaluated to identify any changes in the subjects' disease over a one-year evaluation period. Of the 46 subjects with fundus photographs that were analyzed and scored, 67% of Vitrase-treated subjects had stable ETDRS scores (indicating no measurable disease progression), compared to 38% of saline-treated subjects, 40% of subjects treated with SF6 gas, and 43% of subjects treated with Vitrase plus SF6 gas.

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