Phosphate Binding of Chitosan Chewing Gum in Patients With Chronic Kidney Disease (CKD)

To determine the amount of phosphate recovered into 2 strengths of K2CG chewing gum in a modified formulation (with or without an extender) added to the gum core, in comparison to matching placebo gums.

The current treatment for elevated serum phosphorus levels in chronic kidney disease (CKD) consists of dietary restriction of P and the provision of phosphate binders that act at the level of the intestinal absorption of phosphorus (P) when ingested with meals. This paradigm has proven to be inadequate to achieve normo-phosphatemia as indicated by elevated serum P levels in patients receiving renal replacement therapy.

Salivary phosphate levels are elevated in patients with CKD and salivary P represents a large source of otherwise hidden non-dietary phosphate that is easily absorbed and may contribute to persistent elevations in serum P despite standard therapy.

Savica et al performed a preliminary study, in a small population (n-13) of hyperphosphatemic patients receiving hemodialysis, phosphate restriction and phosphate binders, and given K2CG chewing gum 20 mg. The chewing gum was administered twice per day for 60 minutes during fasting periods (between meals) for 15 days. In addition to a significant reduction in salivary P, serum P was reduced by 2 mg/dL (31%) over the treatment period. Both salivary and serum P returned to baseline values after K2CG discontinuation. The authors concluded that adding salivary P binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in patients receiving renal replacement therapy (RRT).

Given the public health importance of increased P levels in the general population and specifically in patients with chronic kidney disease, it is of great importance to evaluate the ability of a medical food such as K2CG to reduce elevated serum P levels. In patients with CKD receiving RRT it has been estimated that sustained control of serum P may result in an approximate 17% reduction in mortality.

The specific purpose of this study is to compare the total P recovered per piece of chewing gum with 20 mg and 60 mg versions of the reformulated K2CG with or without the extender in the gum core. Additionally, the unique P binding of the reformulated gum will be assessed in comparison with the total P entrapped per piece of chewing gum in the matching placebos.

Subjects will be assigned to one of 3 different groups as shown in the table below. The study will be a single blind study. Subjects will be blinded as to the strength/formulation of the chewing gum and the active/placebo assignment.

Group Active Chewing Week 1 Active Chewing Week 2 20 mg with extender 20 mg Placebo 20 Placebo 60 60 mg with extender 60 mg

Subjects will chew the K2CG gum of a single strength/formulation for 7 days (Active Chewing Week 1) twice a day (BID). K2CG gum must be chewed at least 60 minutes in fasting conditions. This will be followed by a second 7 days of chewing K2CG gum (Active Chewing Week 2) of a different strength/formulation as described above.

There will be no run-in period and no wash out period between Active Chewing Week 1 and Active Chewing Week 2.

• Placebo Comparator: Placebo 20mg
  Intervention: Other: chewing gum
• Active Comparator: K2CG 60 mg extender
  Intervention: Other: chewing gum
• Active Comparator: K2CG 60 mg
  Intervention: Other: chewing gum
• Active Comparator: K2CG 20mg extender
  Intervention: Other: chewing gum
• Active Comparator: K2CG 20mg
  Intervention: Other: chewing gum
• Placebo Comparator: Placebo 60mg
  Intervention: Other: chewing gum

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;
• Subject must be prescribed a diet appropriate for patients with their stage of CKD and must be willing to avoid intentional changes in diet; and
• Subject must have completed the CMD002 clinical trial and is currently receiving hemodialysis.

Exclusion Criteria:

• Subject is receiving or has received an investigational product (or is currently using an investigational device) within 7 days prior to baseline;
• Subject has a known sensitivity to chitin or allergy to shellfish;
• Subject has a clinically significant infection requiring treatment with antibiotics (within 7 days prior to baseline);
• Subject has had an inpatient hospitalization within 7 days prior to baseline with the exception of hospitalizations related to vascular access procedures; In the opinion of the investigator, subject is unable to chew gum for 60 minutes; and
• Subject has an unstable medical condition which in the opinion of the investigator would compromise successful completion of the study;