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Ruboxistaurin May Improve Diabetic Nephropathy: Presented at ADA

By Jill Stein

SAN DIEGO, CA -- June 14, 2005 -- The investigational compound ruboxistaurin mesylate appears to significantly decrease albuminuria in patients with type 2 diabetes and nephropathy on stable doses of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or both.

These findings, from a year-long phase 2 trial, were presented here on June 13^th at the American Diabetes Association's 65^th Annual Scientific Sessions (ADA).

Ruboxistaurin is a selective inhibitor of protein kinase C beta, an enzyme that has been implicated in the underlying process of microvascular damage caused by diabetes. In addition to diabetic nephropathy, the compound is being evaluated for potential use in the treatment of diabetic peripheral neuropathy and diabetic retinopathy.

Katherine Tuttle, MD, director of research, Heart Institute of Spokane, Spokane, Washington, presented the results based on a study of 123 patients who were randomized to ruboxistaurin 32 mg/day or placebo. Patients continued treatment with these agents throughout the trial.

In experimental studies, ruboxistaurin had been shown to improve renal disease, Dr. Tuttle said.

In Dr. Tuttle's study, all subjects had persistent albuminuria despite treatment with stable doses of ACE inhibitors, ARBs, or both for at least 6 months before the start of the trial. Persistent albuminuria was defined as a urinary albumin/creatinine ratio (ACR) of 200 to 2000 mg/g.

After 1 year, ACR decreased significantly by 24% from baseline (P =.02) but the 9% decrease in the placebo group did not reach significance (P =.33). The decrease in albuminuria in the ruboxistaurin group was apparent after 1 month of treatment and remained consistent throughout the trial.

Glomerular filtration rate (GFR) decreased by 4.8 mL/min/year (P =.009) in placebo-treated subjects over 1 year but did not decrease significantly in the ruboxistaurin group (-2.5 mL/min/year, P =.185).

Dr. Tuttle emphasized that while comparisons for both ACR and GFR were not different between the treatment groups, this trial was not designed to determine such a difference and the power for either analysis was less than 20%.

Ruboxistaurin and placebo groups were similar with respect to adverse effects, although more patients in the placebo group had hypertensive episodes requiring intervention.

Overall, ruboxistaurin was well tolerated, however the small sample size and short follow-up period rule out definitive conclusions about safety, Dr. Tuttle said.

Overall, the results suggest that ruboxistaurin may improve upon established therapies for diabetic nephropathy, she concluded.

The study was sponsored by Eli Lilly and Company, Indianapolis, Indiana.


[Presentation title: Effect of Ruboxistaurin on Albuminuria and GFR in Persons With Type 2 Diabetes and Nephropathy. Abstract 223-OR]

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