Bioavailability of Lesinurad and Intravenous [14C]Lesinurad

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Lesinurad 400 mg; Drug: [14C]lesinurad (100 μg per 10 mL)

• Registration Number: NCT02039700
• Lead Sponsor: Ardea Biosciences, Inc.

Brief Summary

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.

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 Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-16
• Study First Submitted QC: 2014-01-16
• Study First Posted: 2014-01-20
• Primary Completion: 2014-02
• Study Completion: 2014-04
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-16
• Last Update Posted: 2014-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lesinurad and [14C]lesinurad	Lesinurad 400 mg	Single oral dose of lesinurad and single infusion of \[14C\]lesinurad
Lesinurad and [14C]lesinurad	[14C]lesinurad (100 μg per 10 mL)	Single oral dose of lesinurad and single infusion of \[14C\]lesinurad

Primary Outcome Measures

Name	Time	Method
Characteristics of bioavailability in terms of lesinurad Pharmacokinetics (PK) profile from plasma.	Day 1 to Day 5	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).
PK profile of [14C]lesinurad from plasma	Day 1 to Day 5	PK profile in terms of Cmax, AUC, t½, MRT, total body clearance (CL), and volume of distribution at steady state (Vss).

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	5 weeks