A Double Blind Randomized Placebo Trial of Maintenance of Normal Serum Phosphorus in CKD

A Double Blind Randomized Placebo Controlled Trial of Maintenance of Normal Serum Phosphorus in Chronic Kidney Disease (CKD)

The purpose of this study is to determine the ability of 3 commercially available phosphorus binders (calcium acetate, sevelamer carbonate, and lanthanum carbonate) to achieve and maintain a phosphorus level in the normal range in patients with chronic kidney disease.

It is the specific aim of this pilot study to assess the feasibility of achieving and maintaining a serum P less than or equal to 3.5 mg/dL (1.13 mmol/L) in patients with eGFR >20 and <45 mL/min with any of the 3 commercially available P lowering agents (calcium acetate, sevelamer carbonate, or lanthanum carbonate). Results of this study will clarify the degree of separation in serum P that can be achieved with the use of P lowering agents and the current standard of care (P binder initiation when P > 5.5 mg/dL or 1.78 mmol/L). Furthermore, this knowledge, combined with analyses of the secondary aims and outcomes of interest, will serve to facilitate the design of a properly powered, randomized, placebo controlled clinical outcomes trial that will firmly establish the necessity of achieving a specific target P in patients with CKD. The secondary aims of this pilot study are to provide insight into the optimal detection of progression of abnormalities in mineral metabolism and their relationship to vascular disease in CKD. The tertiary aim is to evaluate long term outcomes related to phosphorus normalization with respect to renal replacement therapy or death.

Inclusion Criteria:

• Men or women > 18 years of age;
• Has signed and dated the most recent informed consent form approved by an IRB;
• Will, in the opinion of the PI, be compliant with prescribed phosphate binder therapy;
• Must be able to communicate with the investigator, and be able to understand and comply with the requirements of the study;
• Has a life expectancy >12 months;
• An eGFR rate (estimated by the MDRD equation) ≥ 20 and ≤ 45 mL/min/1.73m2 obtained by screening laboratory values and in the opinion of the investigator felt to have CKD without evidence of recent acute kidney injury or unexpected decline in renal function;
• A screening serum phosphorus value > 3.5 mg/dL and ≤ 6.0 mg/dL;
• Must consume a minimum of 2 meals per day and be willing to avoid intentional changes in diet;
• Women of child bearing potential must be practicing an acceptable form of birth control.

Exclusion Criteria:

• Receiving or has received an investigational drug (or is currently using an investigational device) within 30 days prior to baseline;
• Subject is pregnant, is breast feeding or is of child bearing potential and not using acceptable birth control measures;
• Has had a previous renal transplant;
• Has a chronic reliance on enemas or laxatives;
• Has a known sensitivity or previous intolerance to any of the products to be administered during the study;
• Clinical evidence of active malignancy and/or receiving systemic chemotherapy/radiotherapy with the exception of basal cell or squamous carcinoma of the skin;
• Currently has an active infection or is being treated with antibiotics (within 14 days prior to baseline);
• Has been hospitalized within 30 days prior to baseline (with the exception of hospitalizations due to vascular access procedures);
• Any surgical or medical condition which might significantly alter the function of phosphorus binders or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following: Severe gastrointestinal motility disorder,Bowel obstruction,Dysphagia or other disorders of swallowing, Acute peptic ulcer, Ulcerative colitis or Crohn's disease, History of major gastrointestinal tract surgery, Severe malabsorption;
• Currently taking any of the following within 14 days prior to baseline; Calcitriol or its analogs, Cinacalcet hydrochloride, Medications prescribed for the purpose of phosphorus binding;
• Screening serum intact PTH >500 pg/mL;
• Screening corrected calcium < 8.0 mg/dL or > 10.4 mg/dL;
• Uncontrolled hyperlipidemia in the opinion of the PI;
• Initiation of chronic maintenance hemodialysis planned within 12 months;
• Relocation to another area planned within 12 months;
• Has a known history of immunodeficiency diseases, including a positive HIV test result;
• Active drug or alcohol dependence or abuse (excluding tobacco use) within the 12 months prior to dosing or evidence of such abuse;
• Evidence of active liver disease with AST or ALT levels greater than 3X the upper limit of normal;
• Has had a major cardiovascular event within 180 days of screening.