Safety and Pharmacokinetic Study of C13-URA in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and establish the pharmacokinetic (PK) profile of C13-URA in healthy volunteers

Detailed Description
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The C13-URA Breath Test Kit is intended to be used as a diagnostic tool to identify rapid and/or delayed gastric emptying in patients who have upper GI symptoms such as stomach pain, fullness, early satiety, vomiting, etc., and who have suspected gastric emptying abnormalities such as gastroparesis or dumping syndrome. This study will be a double-blind, placebo-controlled, 3-period safety and PK study of 13C-uracil administered as a single oral dose of 50 mg at step 1 (Period 1), 100 mg at step 2 (Period 2), and 200 mg at step 3 (Period 3) in the form of a semi-solid meal to subjects following at least a 10-hour fast from food and 2-hour fast from water. Dosing will be followed by a 6-hour fast from food and a 4-hour fast from water. There will be a washout of at least 7 days between doses. The objectives of this study are as follows; 1)to evaluate the safety of 13C-uracil in a semi-solid meal in healthy volunteers, 2)to establish the pharmacokinetic profile of 13C-uracil in a semi-solid meal in healthy volunteers, 3)to assess the correlation between plasma concentration of 13C-uracil and urinary excretion of 13C-uracil, 4)to evaluate the reproducibility (intra/inter-individual variance) of the breath test, 5)to determine the dose for 13C-uracil that facilitates adequate Δ13C in breath expired by healthy volunteers

Official Title
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A Phase I, Double-Blind, Placebo-Controlled, Randomized, 3-Period, Safety and Pharmacokinetic Study of 13C-uracil in a Semi-solid Meal at Single Oral Doses of 50, 100, and 200 mg in Healthy Volunteers

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: [2-13C] uracil
* Drug: [2-13C] uracil, placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index [range is 18.5 to 29.9 kg/m2] In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs Exclusion Criteria: Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the investigator) History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed) History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically significant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C13-URA<br>administered C13-URA 50, 100, 200mg in same subjects | Drug: [2-13C] uracil<br>* po, in the form of semi-solid meal, granules, once a period<br>|
| Placebo Comparator: Placebo<br>2 same subjects | Drug: [2-13C] uracil, placebo<br>* po, in the form of semi-solid meal, granules, once a period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters | Pharmacokinetic endpoints will include apparent clearance (CL/F), AUCt, AUC∞, Cmax, tmax, and t1/2,Z for 13C-uracil and its metabolites. The PK linearity and correlation between plasma concentration and urine excretion will be evaluated. Expired 13CO2 concentrations (Δ13C) will be converted to 13CO2-excretion(% dose/hr) to assess breath PK parameters (AUCt, AUC∞, Cmax, tmax, λZ, and t1/2,Z). | 6 hours |