Chronic Kidney Disease, Hyperphosphatemia
Conditions
Keywords
Hyperphosphatemia, chronic kidney disease, salivary phosphorus
Brief 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.
Detailed description
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.
Interventions
OTHERFOSTRAP Chewing Gum
20 mg BID
OTHERPlacebo chewing gum
Sponsors
CM&D Pharma Limited
Denver Nephrologists, P.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in serum phosphorus from baseline to Day 29 | Day 1 and Day 29 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects whose serum phosphorus reduction from baseline to Day 29 is greater than or equal to 0.5 mg/dL | Day 1 and Day 29 |
| Proportion of subjects whose serum phosphorus reduction from baseline to Day 29 is greater than or equal to 1.5 mg/dL | Day 1 and Day 29 |
| Change in salivary phosphorus from baseline to Day 29 | Day and Day 29 |
| For subjects with ESRD absolute and relative difference between serum phosphorus (baseline to Day 29)- (Day 57 to day 71) | Day 29, Day 57, Day 71 |
| Change in salivary phosphorus from Day 57 to Day 71 | Day 57 and Day 71 |
| Change in serum phosphorus from Day 57 to day 71 for subjects with ESRD | Day 57 and Day 71 |
Countries
United States
Outcome results
None listed