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

A Double Blind, Randomized, Placebo Controlled Trial to Evaluate the Efficacy and Safety of FOSTRAP Chewing Gum in Patients With Chronic Kidney Disease and Hyperphosphatemia.

The phosphorus content in saliva is increased in chronic kidney disease. We hypothesize that a chewing gum that binds salivary phosphorus would be a novel, effective agent to reduce serum levels of phosphorus in patients with chronic kidney disease. We are testing this hypothesis using a chewing gum called FOSTRAP which has been shown to be effective in a small, non-randomized study in patients with chronic kidney disease on hemodialysis.

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:

1. Men or women > 18 years of age;

2. The subject has voluntarily signed and dated the most recent informed consent form approved by an Institutional Review Board (IRB);

3. The subject will, in the opinion of the investigator, be compliant with prescribed therapy;

4. Subject must be able to communicate and be able to understand and comply with the requirements of the study;

5. 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;

6. For subjects with CKD not on dialysis- a screening serum phosphorus value greater than or equal to 4.5 mg/dL;

7. 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;

8. 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;

9. Subjects with ESRD must have an historical URR ≥ 65% for at least 4 weeks prior to baseline;

10. All subjects must have NO change in prescribed dose or frequency of any of the following medications ≥ 14 days prior to baseline:

    1. Phosphate binding products including prescribed and over-the counter
    2. Oral or injectable active vitamin D
    3. Oral nutritional vitamin D
    4. Calcimimetics
    5. Calcium supplements
    6. Anti-osteoporotic medication (e.g. bisphosphonates)

11. 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

12. Subjects must have a screening salivary flow rate by Saxon test ≥ 1 g/2 min.

Exclusion criteria:

1. Receiving or has received an investigational product (or is currently using an investigational device) within 28 days prior to baseline;

2. Known sensitivity to chitin or allergy to shellfish;

3. Clinical evidence of active malignancy and/or receiving systemic chemotherapy/radiotherapy with the exception of basal cell or squamous carcinoma of the skin;

4. Clinically significant infection requiring treatment with antibiotics (within 7 days prior to baseline);

5. Inpatient hospitalization within 14 days prior to baseline with the exception of hospitalizations related to vascular access procedures;

6. Planned surgical intervention for secondary hyperparathyroidism;

7. In the opinion of the investigator, inability to chew gum for 60 minutes;

8. Planned relocation to another area within the next 4 months;

9. Subject has a known history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result;

10. Active drug or alcohol dependence or abuse (excluding tobacco use) in the opinion of the principal investigator;

11. Unstable medical condition which in the opinion of the investigator would compromise successful completion of the study;

12. Known active liver disease with AST or ALT levels greater than 3X the upper limit of normal; and

13. Subject has had a major cardiovascular event within 90 days of screening. The investigator should be guided by evidence of any of the following;

    1. Acute myocardial infarction
    2. Acute cerebral vascular event
    3. Vascular surgical intervention
    4. Coronary Revascularization
    5. Decompensated congestive heart failure