Bioavailability of Lesinurad and Intravenous [14C]Lesinurad

A Phase 1, Open-Label Study to Assess the Absolute Bioavailability of a Single Oral Dose of Lesinurad With Respect to an Intravenous Micro Tracer Dose of [14C]Lesinurad in Healthy Adult Male Subjects

This study will assess the absolute bioavailability of a single oral dose of lesinurad and evaluate the pharmacokinetic (PK) parameters of lesinurad and [14C]lesinurad in healthy adult male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lesinurad 400 mg; Drug: [14C]lesinurad (100 μg per 10 mL)

Detailed Description

In this study a single dose of lesinurad will be administered after an overnight fast followed by a single 15-minute infusion of a radiolabeled intravenous micro tracer dose of [14C]lesinurad to assess the in vivo performance of lesinurad.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject has a body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m2.
• Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment

Exclusion Criteria:

• Subject has a history or suspicion of kidney stones.
• Subject has undergone major surgery within 3 months prior to Screening.
• Subject donated blood or experienced significant blood loss (>450 mL) within 12 weeks prior to Screening or gave a plasma donation within 4 weeks prior to Screening.
• Subject has inadequate venous access or unsuitable veins for repeated venipuncture.
• Subject does not have a normal or clinically acceptable physical examination, per the Investigator's judgment.
• Subject has clinically relevant abnormalities in blood pressure, heart rate, or body temperature, per the Investigator's judgment.
• Subject has Screening clinical safety laboratory parameters (serum chemistry, hematology, or urinalysis) that are outside the normal limits and are considered clinically significant by the Investigator.
• Subject has clinically relevant abnormalities in 12-lead electrocardiogram, per the Investigator's judgment.
• Subject has a Screening serum urate level > 7 mg/dL.
• Subject had radiation exposure that exceeds 5 mSv in the last 12 months or 10 mSv in the last 5 years. This includes radiation exposure from the present study or other clinical studies, including diagnostic X-rays and other medical exposures but excluding exposure to background radiation. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lesinurad and [14C]lesinurad; Single oral dose of lesinurad and single infusion of [14C]lesinurad	Drug: Lesinurad 400 mg; Drug: [14C]lesinurad (100 μg per 10 mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of bioavailability in terms of lesinurad Pharmacokinetics (PK) profile from plasma.	PK profile in terms of maximum observed concentration (Cmax), time of occurrence of maximum observed concentration (Tmax), area under the concentration-time curve (AUC), apparent terminal half-life (t½), mean residence time (MRT), mean absorption time (MAT), and absolute bioavailability (F).	Day 1 to Day 5
PK profile of [14C]lesinurad from plasma	PK profile in terms of Cmax, AUC, t½, MRT, total body clearance (CL), and volume of distribution at steady state (Vss).	Day 1 to Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	5 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 16, 2014
• First Submitted That Met QC Criteria: January 16, 2014
• First Posted (Estimate): January 20, 2014

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 16, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Lesinurad
• Other Study ID Numbers: RDEA594-131