Safety and Pharmacokinetic Study of C13-URA in Healthy Volunteers

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

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

Study Overview

• Status: Completed
• Conditions: Gastroparesis
• Intervention / Treatment: Drug: [2-13C] uracil; Drug: [2-13C] uracil, placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Pharmacology, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Stephen D Flach, MD, PhD, CPI, Covance Clinical Pharmacology, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: February 18, 2010
• First Submitted That Met QC Criteria: February 23, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Estimate): July 19, 2010
• Last Update Submitted That Met QC Criteria: July 16, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Gastroparesis
• Other Study ID Numbers: URA-09-001