Effect of Phosphate Binders on Markers of Vascular Health in Chronic Kidney Disease Stages 3 and 4

• Change in vascular calcification biomarker levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change in endothelial dysfunction biomarker levels. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• Change in inflammatory biomarker levels [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Chronic kidney disease (CKD) patients often have high levels of a substance called fibroblast growth factor-23 (FGF-23), a phosphorus excreting hormone, which has been related to heart disease. As kidney function declines, less phosphorus is removed by the kidneys and as a result phosphorus accumulates in the blood. In response to elevated phosphorus levels, more FGF-23 is released to help facilitate the excretion of extra phosphorus into the urine. In addition to effects on FGF-23, increased phosphorus levels can lead to calcification (hardening) of the blood vessels in the CKD population.

Phosphate binding medicines are used in CKD patients to lower the amount of phosphorus absorbed by the stomach and intestines after eating meals and snacks. In patients with CKD, studies have shown that phosphate binders can lower FGF-23 levels in the blood. Lowering FGF-23 levels in CKD patients may also lower substances in the blood that cause calcification of blood vessels in the CKD population.

This study is being done to determine if using phosphate binders, either sevelamer carbonate or calcium acetate, in the earlier stages kidney disease (before dialysis) can decrease FGF-23 and biomarkers (substances in the blood) associated with hardening of the blood vessels and heart disease.

• Drug: Sevelamer carbonate
  Sevelamer carbonate 1,600 mg three times daily with meals
  Other Name: Renvela
• Drug: Calcium acetate
  Calcium acetate 1,334 mg three times daily with meals for 12 weeks
  Other Name: Phoslo

• Experimental: Sevelamer carbonate
  1,600 mg (2 x 800 mg) three times daily with meals for a total of 12 weeks
  Intervention: Drug: Sevelamer carbonate
• Active Comparator: Calcium acetate
  1,334 mg (2 x 667 mg) three times daily with meals for a total of 12 weeks
  Intervention: Drug: Calcium acetate

Inclusion Criteria:

• Males or females ≥ 18 years of age at start of screening
• CKD stage 3 or 4 defined by an eGFR 15 - 60 mL/min/1.73m2
• Not expected to start dialysis for 8 months
• Serum intact PTH < 500 pg/mL during screening period
• On a stable ACE inhibitor/ARB regimen for 30 days prior to screening

Exclusion Criteria:

• History of any of the following diseases: congestive heart failure, MI within the last 6 months, cerebrovascular accident, significant valvular disease, malignancy
• Currently receiving erythropoiesis stimulating agent or IV iron therapy
• History of inflammatory/autoimmune disease
• History of polycystic kidney disease
• HIV positive or AIDS
• Pregnant or breastfeeding
• Receiving activated Vitamin D analogs, nutritional vitamin D agents > 2,000 IU/day, or calcimimetics with in the last 3 months
• Significant GI disorder
• Proteinuria >3.5 g/24 hours

• Albany Medical College
• Genzyme