Press Release Source: Abbott On Friday March 4, 2011, 9:00 am EST

ABBOTT PARK, Ill., March 4, 2011 /PRNewswire/ — Results from a Phase 2, 8-week dose-ranging study using low doses of atrasentan in patients with diabetic kidney disease were published this week in the Journal of the American Society of Nephrology. The published study results suggest that atrasentan, used in conjunction with renin-angiotensin system (RAS) inhibitors, may reduce albuminuria (presence of protein in urine) for patients with type 2 diabetes.

Atrasentan is a highly selective endothelin-A receptor (ETAR) antagonist under investigation as a potential treatment for diabetic kidney disease.

Key findings from the 8-week study of three doses of atrasentan (0.25 mg, n=22; 0.75 mg, n=22; 1.75 mg, n=22) vs. placebo (n=23) were:

• Atrasentan significantly reduced urine albumin-to-creatinine ratio (UACR) in the 0.75 mg and 1.75 mg groups vs. placebo (P=0.001 and P=0.011 by repeated measures, respectively). The 0.25 mg dose had no significant effect
• Reduction from baseline to final UACR was 21%, 42%, and 35% in the 0.25 mg, 0.75 mg and 1.75 mg groups vs. 11% in placebo (P=0.291, P=0.023 and P=0.073, respectively).
• A significantly larger proportion of subjects achieved >40% reduction in UACR from baseline in the 0.75 mg group vs. placebo (50% vs 17% respectively, P=0.029). The proportion of patients in the 0.25 mg and 1.75 mg groups (30% and 38% respectively) did not reach statistical significance.
• Peripheral edema was the most common adverse event (14%, 18% and 46% for 0.25, 0.75 and 1.75 mg with P=0.007 for 1.75 mg vs. 9% in placebo). other adverse events that occurred in >5% of patients and at a rate >5% vs. placebo included dizziness, urinary tract infection, headache and hypoglycemia. due to the small numbers of patients in each treatment group and the low event rates, the significance of these other adverse events is unknown.

“Current standard of care modestly slows the progression of the disease and previous studies with standard of care have shown an association with albuminuria reduction and a slowing of disease progression,” said Donald E. Kohan, M.D., Ph.D., Professor of Medicine, Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah and lead investigator for the study. “These early study results suggest that atrasentan may have an additional therapeutic role for albuminuria reduction when added to the current standard of care for patients with type 2 diabetes.”

“Chronic kidney disease and diabetic kidney disease are growing healthcare issues. New treatments that could potentially alter the progression of the disease are needed,” said James Stolzenbach, Ph.D., divisional vice president, Dyslipidemia and Renal, Abbott. “Abbott looks forward to continued study of atrasentan in longer, outcome-driven clinical trials.”

Study Objectives and Design

The study was a double-blind, dose-ranging, placebo-controlled study of 89 diabetic subjects with nephropathy on stable doses of renin-angiotensin system (RAS) inhibitors for >2 months with urinary albumin-to-creatinine ratio (UACR) of 100-3000 mg/g, eGFR >20 mL/min/1.73m2, and NT-pro-BNP