Safety and Pharmacokinetic Study of C13-URA in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT01074710
• Recruitment Status: Completed
• First Posted: February 24, 2010
• Last Update Posted: July 19, 2010
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by: Otsuka Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Gastroparesis	Drug: [2-13C] uracil; Drug: [2-13C] uracil, placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: 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
• Study Start Date: February 2010
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. PK parameters [ Time Frame: 6 hours ]
   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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Wisconsin

Covance Clinical Pharmacology, Inc.

Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

Otsuka Pharmaceutical Co., Ltd.

Investigators

• Principal Investigator: Stephen D Flach, MD, PhD, CPI; Covance Clinical Pharmacology, Inc.

More Information

• Responsible Party: Suguru Akamatsu/Director, R&D Department, Diagnostic Division
• ClinicalTrials.gov Identifier: NCT01074710
• Other Study ID Numbers: URA-09-001
• First Posted: February 24, 2010
• Last Update Posted: July 19, 2010
• Last Verified: May 2010

Additional relevant MeSH terms:

Gastroparesis; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations