Double Blind Randomized Placebo Controlled Trial of FOSTRAP Chewing Gum in Patients With CKD and Hyperphosphatemia

A double-blind, randomized, placebo, controlled trial with an open label extension for those subjects with end stage renal disease (ESRD).

Patients with ESRD will be randomized to receive either FOSTRAP™ 20 mg BID, FOSTRAP™ 40 mg BID or matching placebo 2x/day. All subjects will participate in a 4 week chewing period followed by a 4 week follow up period. All subjects will then enter an open label 2 week extension phase in which they will receive FOSTRAP™ 20 mg TID.

Patients with chronic kidney disease (CKD) not on dialysis will receive either FOSTRAP™ 20 mg 3x/day or placebo TID for 4 weeks followed by a 4 week follow up period.

Inclusion criteria

• Men or women > 18 years of age;
• The subject has voluntarily signed and dated the most recent informed consent form approved by an Institutional Review Board (IRB);
• The subject will, in the opinion of the investigator, be compliant with prescribed therapy;
• Subject must be able to communicate and be able to understand and comply with the requirements of the study;
• For subjects with CKD not on dialysis- kidney function at any stage that in the opinion of the investigator is stable and not expected to initiate dialysis within 3 months;
• For subjects with CKD not on dialysis- a screening serum phosphorus value greater than or equal to 4.5 mg/dL;
• For subjects with ESRD - a screening serum phosphorus value greater than or equal to 4.6 mg/dL and less than or equal to 9.0 mg/dL and one of the two conditions: A mean historical value of the most recent 2 phosphorus measurements ≥ 4.6 and less than or equal to 9.0 mg/dL at the time of written informed consent or A second screening serum phosphorus value greater than or equal to 4.6 mg/dL and less than or equal to 9.0 mg/dL performed not less than 7 days from the date of the previous screening;
• In the opinion of the investigator, subjects with ESRD must be prescribed a stable dialysis regimen (3x/week) for ≥ 4 weeks prior to baseline and must have a stable dialysis access;
• Subjects with ESRD must have an historical URR ≥ 65% for at least 4 weeks prior to baseline;
• All subjects must have NO change in prescribed dose or frequency of any of the following medications ≥ 14 days prior to baseline:

• Phosphate binding products including prescribed and over-the counter
• Oral or injectable active vitamin D
• Oral nutritional vitamin D
• Calcimimetics
• Calcium supplements
• Anti-osteoporotic medication (e.g. bisphosphonates)
• Subject must be prescribed a diet appropriate for patients with their stage of kidney disease, and must be willing to avoid intentional changes in diet; and
• Subjects must have a screening salivary flow rate by Saxon test ≥ 1 g/2 min.

Exclusion criteria

• Receiving or has received an investigational product (or is currently using an investigational device) within 28 days prior to baseline;
• Known sensitivity to chitin or allergy to shellfish;
• Clinical evidence of active malignancy and/or receiving systemic chemotherapy/radiotherapy with the exception of basal cell or squamous carcinoma of the skin;
• Clinically significant infection requiring treatment with antibiotics (within 7 days prior to baseline);
• Inpatient hospitalization within 14 days prior to baseline with the exception of hospitalizations related to vascular access procedures;
• Planned surgical intervention for secondary hyperparathyroidism;
• In the opinion of the investigator, inability to chew gum for 60 minutes;
• Planned relocation to another area within the next 4 months;
• Subject has a known history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result;
• Active drug or alcohol dependence or abuse (excluding tobacco use) in the opinion of the principal investigator;
• Unstable medical condition which in the opinion of the investigator would compromise successful completion of the study;
• Known active liver disease with AST or ALT levels greater than 3X the upper limit of normal; and
• Subject has had a major cardiovascular event within 90 days of screening. The investigator should be guided by evidence of any of the following;

• Acute myocardial infarction
• Acute cerebral vascular event
• Vascular surgical intervention
• Coronary Revascularization
• Decompensated congestive heart failure