SAN DIEGO — Ruboxistaurin, a specific protein kinase C beta inhibitor, had favorable effects on albuminuria and renal function in patients with diabetic nephropathy, according to results from the first human trial of the drug.
“Ruboxistaurin is a promising novel therapy that may improve upon established therapies for diabetic nephropathy,” Katherine R. Tuttle, M.D., said at the annual scientific sessions of the American Diabetes Association.
A lot of data show “that diabetic nephropathy, even in advanced stages, is potentially reversible. Perhaps this builds that bit of evidence. Large-scale trials should be performed to confirm its effectiveness and safety.”
Developed by Eli Lilly & Co., ruboxistaurin is the first of the specific protein kinase C beta inhibitors being investigated for the treatment of diabetic peripheral neuropathy, diabetic retinopathy, and diabetic nephropathy.
In a year-long multicenter, randomized, double-blind trial funded by Lilly, Dr. Tuttle and her associates randomized 123 subjects to receive ruboxistaurin 32 mg/day or placebo. Study participants who were taking ACE inhibitors, angiotensin receptor blockers, or both remained on the drugs for the entire trial.
Over the course of 12 months, investigators at 17 sites in the United States obtained periodic measurements of the participants' urinary albumin/creatinine ratio (ACR), blood pressure, estimated glomerular filtration rate (GFR), and hemoglobin A1c levels.
By month 12, the mean ACR had decreased by 24% among subjects in the ruboxistaurin group but had not changed in the placebo group, reported Dr. Tuttle of Providence Medical Research Center and The Heart Institute of Spokane, Washington.
The change in urinary ACR in the ruboxistaurin group appeared as early as 1 month into the study and was maintained over the 12-month trial. The mean estimated GFR declined by a mean of 4.8 mL/min per year in the placebo group but did not change significantly in the ruboxistaurin group.
Blood pressure and hemoglobin A1c levels did not differ significantly between the two groups over the study period.
The most frequently reported adverse event was hypertension, which required intervention in 8% of subjects in the placebo group, compared with none in the ruboxistaurin group.
Dr. Tuttle, who is a paid consultant to Lilly, noted that it will take “at least several hundred if not more” subjects per treatment arm to confirm the findings in a future trial.
Diabetic nephropathy develops in about 40% of people with type 2 diabetes and is responsible for 40%–50% of incident end-stage renal disease in the United States.