PD Study to Assess Phosphate Binding Characteristics of K2CG Chewing Gum

Study Overview
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Brief Summary
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The specific purpose of this study is to describe the characteristics of the K2CG chewing gum, specifically as it relates to duration of gum chewing (exposure), timing of gum chewing in relation to a meal, and dose of K2CG chewing gum.

Detailed Description
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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 one placebo chewing gum (1.7 g). Thirty-six subjects will be enrolled across three renal function group based on estimated glomerular filtration rate. Study assessments will occur over four study visit days (Visit 2, Visit 3, Visit 4, and Visit 5). 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 and one placebo: 20 mg dose at Visit 2, 1.7 g placebo at Visit 3, 40 mg dose at Visit 4, and 60 mg dose at Visit 5. 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.

Official Title
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A Single Blind Pharmacodynamic Study to Assess the Phosphate Binding Characteristics of K2CG Chewing Gum

Conditions
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Hyperphosphatemia, Chronic Kidney Disease

Intervention / Treatment
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* Other: K2CG chewing gum
* Other: K2CG chewing gum
* Other: K2CG chewing gum
* Other: K2CG chewing gum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women > 18 years of age; Must have no dietary restriction that would preclude eating standardized meal (both a meat based and vegan option available) The subject has voluntarily signed and dated the most recent informed consent form approved by an Institutional Review Board (IRB). Must be able to chew gum for at least 60 minutes. Must have historical eGFR appropriate for the study. Exclusion Criteria: Receiving or has received an investigational product (or is currently using an investigational device) within 30 days prior to Visit 2; Evidence of active (clinically significant) infection at the time of study enrollment (in the opinion of the investigator); Dental work within 48 hours of enrollment (Visit 2); and Known sensitivity to chitin, or allergy to shellfish

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

Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chewing Arm 1<br> | Other: K2CG chewing gum<br>* Fasting: Chew gum 15 minutes Post meal: Begin chewing 45 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum 30 minutes Post meal: Begin chewing 30 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 45 minutes Post meal: Begin chewing gum 15 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 60 minutes Post meal: Being chewing gum 5 minutes post meal<br>|
| Placebo Comparator: Chewing Arm 2<br> | Other: K2CG chewing gum<br>* Fasting: Chew gum 15 minutes Post meal: Begin chewing 45 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum 30 minutes Post meal: Begin chewing 30 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 45 minutes Post meal: Begin chewing gum 15 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 60 minutes Post meal: Being chewing gum 5 minutes post meal<br>|
| Active Comparator: Chewing Arm 3<br> | Other: K2CG chewing gum<br>* Fasting: Chew gum 15 minutes Post meal: Begin chewing 45 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum 30 minutes Post meal: Begin chewing 30 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 45 minutes Post meal: Begin chewing gum 15 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 60 minutes Post meal: Being chewing gum 5 minutes post meal<br>|
| Active Comparator: Chewing Arm 4<br> | Other: K2CG chewing gum<br>* Fasting: Chew gum 15 minutes Post meal: Begin chewing 45 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum 30 minutes Post meal: Begin chewing 30 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 45 minutes Post meal: Begin chewing gum 15 minutes post meal<br>Other: K2CG chewing gum<br>* Fasting: Chew gum for 60 minutes Post meal: Being chewing gum 5 minutes post meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total phosphate bound per gum piece fasting | patients will be assigned to treatment arms of varying chewing duration fasting and the total phosphorous bound per piece of chewing gum will be assessed. each patient will recieve (in random order) gum with placebo, 20 mg, 40 mg, and 60 mg chitosan content | 15 min, 30 min, 45 min, 60 min post chewing | 
| total phosphate bound per piece of gum post meal | Each subject will begin chewing at the assigned time post meal exposure and chew for 30 minutes. total phosphorus bound per piece of gum will be assessed. each patient will recieve (in random order) gum with placebo, 20 mg, 40 mg, and 60 mg chitosan content | 5 min, 15 min, 30 min, 45 minutes post meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, phosphorus, phosphate, saliva, K2CG, medical food, chitosan