double blind randomized placebo controlled trial of fostrap chewing gum in patients with ckd and hyperphosphatemia

Conditions: Hyperphosphatemia; Chronic Kidney Disease

Summary: 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.

Eligibility criteria:
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

Keywords: hyperphosphatemia chronic kidney disease salivary phosphorus