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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Hyperphosphatemia, Chronic Kidney Disease

Intervention / Treatment
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* Other: FOSTRAP Chewing Gum
* Other: FOSTRAP Chewing Gum
* Other: FOSTRAP Chewing Gum
* Other: FOSTRAP Chewing Gum
* Other: Placebo chewing gum


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ESRD: FOSTRAP Chewing Gum<br> | Other: FOSTRAP Chewing Gum<br>* 20 mg BID<br>Other: FOSTRAP Chewing Gum<br>* 40 mg BID<br>Other: FOSTRAP Chewing Gum<br>* 20 mg TID<br>|
| Active Comparator: CKD: FOSTRAP Chewing Gum<br> | Other: FOSTRAP Chewing Gum<br>* 20 mg TID<br>|
| Placebo Comparator: ESRD Matching Placebo<br> | Other: Placebo chewing gum<br> <br> |
| Placebo Comparator: CKD Matching Placebo<br> | Other: Placebo chewing gum<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum phosphorus from baseline to Day 29 |  | Day 1 and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in salivary phosphorus from baseline to Day 29 |  | Day and Day 29 | 
| 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 serum phosphorus from Day 57 to day 71 for subjects with ESRD |  | Day 57 and Day 71 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperphosphatemia, chronic kidney disease, salivary phosphorus