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Positive final results reported from phase II study of diabetic nephropathy therapy
(Heart Disease Weekly)
Keryx Biopharmaceuticals, Inc. (KERX) announced positive final efficacy results from its phase II study entitled, "An exploratory, randomized, double-blind, multiple dose study of KRX-101 (sulodexide gelcaps) for the treatment of type 2 diabetic nephropathy patients with persistent microalbuminuria."
In a presentation at the American Society of Nephrology's Renal Week conference in Philadelphia, Pennsylvania, Edmund J. Lewis, MD, head of the collaborative study group and the principal investigator of the phase II study, presented final data from the study.
The phase II study was designed as a pilot for the fully powered pivotal phase III study, which is ongoing.
In this phase II study, two doses of KRX-101 (200 mg and 400 mg) were compared to placebo in patients with diabetic microalbuminuria on maximal therapy with an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were treated with KRX-101 or placebo for 6 months and followed for an additional 2 months post-treatment. Patients were randomized 1:1:1, placebo, 200 mg and 400 mg of KRX-101, respectively.
In this phase II study, the primary endpoint for the study was the percentage of patients achieving "Therapeutic Success" at 6 months. This is also the endpoint in the protocol for the KRX-101 phase III clinical trial now recruiting patients, and which was agreed to with the U.S. Food & Drug Administration (FDA) under an SPA. A patient is considered a "Therapeutic Success" if he or she achieves one of the following outcomes following 6 months on study:
(1) Fifty percent reduction in albumin to creatinine ratio or "ACR" -- ACR is a standard measurement used to assess the level of kidney disease in these patients. ACR measures the level of albumin protein in urine, also referred to as "albuminuria," or
(2) Normalization of ACR with at least a 25% reduction in ACR-in this study the normal laboratory range for albuminuria was defined as less than 20 mg of albumin to 1g of creatinine.
A total of 149 patients were randomized into the study. All patients evaluable for Therapeutic Success at 6 months (i.e. all patients with a baseline ACR and a 6-month ACR) were included in the intent to treat analysis, for a total of 136 patients in the intent to treat population. All patients in the intent to treat population that at baseline were within the target eligibility range of microalbuminuria as defined in the protocol (ACR 20 mg/G to 200 mg/G) were included in the per protocol analysis, for a total population of 117 patients in the per protocol population.
There were no serious adverse events that were deemed by the investigators to be related, probably related or possibly related to the study drug. A full analysis of the safety database will be conducted in the coming months.
The phase III portion of the program, entitled "The effect of sulodexide in patients with type 2 diabetes and microalbuminuria," is a randomized, double- blind, placebo-controlled study, comparing 200 mg daily of KRX-101 versus placebo, with a 1:1 randomization between the two arms. The objective of this study is to determine the safety and efficacy of sulodexide in the treatment of patients with type 2 diabetes and persistent microalbuminuria, despite being treated with a maximum approved or tolerated dose of an angiotensin II receptor blocker (ARB) or ACEi.
The phase IV portion of the program, entitled "The effect of sulodexide in overt type 2 diabetic nephropathy," is a randomized, double-blind, placebo- controlled study, comparing 200 mg daily of KRX-101 and placebo, with a 1:1 randomization between the two arms, in patients with persistent macroalbuminuria or overt nephropathy. The objective of this study is to determine the efficacy of sulodexide in reducing the rate of progression of renal disease and adverse clinical sequelae in patients with diabetic nephropathy due to type 2 diabetes, despite being treated with a maximum approved or tolerated dose of an ARB.
The SPA process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application.
The Collaborative Study Group, the largest standing renal clinical trials group, is composed of academic and tertiary care physician-researchers interested in collaborative clinical trials investigating new therapeutic approaches in the treatment of kidney disease.
KRX-101 is an oral heparinoid for the treatment of diabetic nephropathy, a life-threatening kidney disease caused by diabetes. Keryx holds an exclusive license to KRX-101 in the territories of North America, Japan, Australia, Israel and certain other markets.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer.
This article was prepared by Heart Disease Weekly editors from staff and other reports. Copyright 2005, Heart Disease Weekly via NewsRx.com.
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