PD Study to Assess Phosphate Binding Characteristics of K2CG Chewing Gum

Previous studies have demonstrated that salivary phosphate levels are elevated in patients
with CKD and that there is a direct and linear correlation between serum phosphorus and
salivary phosphorus. K2CG chewing gum may provide an alternative approach to treating
patients with elevated phosphate levels. However, data regarding the pharmacodynamic effect
of the K2CG chewing gum on salivary phosphorus is lacking; as such, this study seeks to
examine the phosphate binding characteristics of K2CG chewing gum with 2 different amounts
of chitosan and varying exposure time in the fasting and fed condition.

A precise knowledge of the pharmacodynamic effect of the K2CG chewing gum on salivary
phosphorus is expected to provide information necessary to plan and conduct a subsequent
interventional trial with K2CG chewing gum in patients with both Chronic Kidney Disease and
ESRD. Specifically, quantification of the amount of salivary phosphorus that binds to 3
formulations of chitosan loaded chewing gum (20 mg, 40 mg and 60 mg) with varying exposure
times will inform the optimal duration of exposure relative to gum size. The effect of gum
size will be further explored via the use of two different sizes of placebo chewing gum (1.7
g and 2.0 g sizes). Additionally it is a specific aim of this study to assess whether
chewing gum in the fasted vs. fed state affects the binding characteristics of chitosan
loaded chewing gum.

This study is a pharmacodynamic study to characterize the phosphate binding capabilities of
three different doses of K2CG chewing gum (20mg, 40mg, 60mg) and two different sizes of
placebo chewing gum (1.7 g and 2.0 g). Thirty-six subjects will be enrolled across three
renal function groups (Stage 3, Stage 4, and Stage 5) based on estimated glomerular
filtration rate.

Study assessments will occur over five study visit days (Visit 2, Visit 3, Visit 4, Visit 5
and Visit 6). Fasting study procedures will occur in the morning of each visit day, and
non-fasting procedures will occur following the administration of a standardized meal on the
same day. All subjects will receive three doses of K2CG chewing gum, plus two different
sizes of placebo: 20 mg dose at Visit 2, 1.7 g placebo at Visit 3, 40 mg dose at Visit 4,
2.0 g placebo at Visit 5 and 60 mg placebo at Visit 6. Subjects will not be aware of the
specific gum dose or size at any study visit (single blind). The duration of gum chewing and
timing of salivary collections will vary within each group.

Saliva will be collected at specified time points throughout the trial. Fasting salivary
phosphorus must be collected with nothing to eat or drink for at least 2 hours.