NSAID Drug Interaction Study

Phase 1

Completed

• Conditions: Gout
• Interventions: Drug: lesinurad 400 mg; Drug: naproxen 250 mg; Drug: indomethacin 25 mg

• Registration Number: NCT01884272
• Lead Sponsor: Ardea Biosciences, Inc.

Brief Summary

This is a drug-drug interaction study in healthy volunteers to evaluate the potential pharmacokinetic (PK) effects of non-steroidal anti-inflammatory drugs on lesinurad and leinurad on the non-steroidal anti-inflammatory drugs.

Detailed Description

Naproxen and indomethacin are non-steroidal anti-inflammatory drugs (NSAIDs) used both prophylactically for the prevention of, and as a treatment for, acute gout flares. RDEA594-126 is an open-label study designed to assess the potential effect of multiple doses of naproxen and indomethacin on the single-dose PK of lesinurad, and to assess the potential effect of multiple doses of lesinurad on the multiple-dose PK of naproxen and indomethacin.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-06-18
• Study First Submitted QC: 2013-06-20
• Study First Posted: 2013-06-24
• Primary Completion: 2013-08
• Study Completion: 2013-10
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-06
• Last Update Posted: 2013-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

• Subject has a body weight ≥ 50 kg (110 lbs) and a body mass index (BMI) ≥ 18 and ≤ 30 kg/m2.
• Subject is free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations or procedures.
• Subject has no clinically relevant abnormalities in vital signs, ECG, physical examination or safety laboratory values.

Exclusion Criteria

• Subject has clinically significant pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders.
• Subject has a history or suspicion of kidney stones.
• Subject has a history of asthma.
• Subject has undergone major surgery within 3 months prior to Day 1.
• Subject has donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to the Screening visit.
• Subject has inadequate venous access or unsuitable veins for repeated venipuncture.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Lesinurad 400 mg and naproxen 250 mg	lesinurad 400 mg	Lesinurad once daily (qd) Day 1, naproxen twice daily (bid) Day 2-6, lesinurad qd with naproxen bid Day 7-14.
Lesinurad 400 mg and naproxen 250 mg	naproxen 250 mg	Lesinurad once daily (qd) Day 1, naproxen twice daily (bid) Day 2-6, lesinurad qd with naproxen bid Day 7-14.
Lesinurad 400 mg and indomethacin 25 mg	lesinurad 400 mg	Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14.
Lesinurad 400 mg and indomethacin 25 mg	indomethacin 25 mg	Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14.

Primary Outcome Measures

Name	Time	Method
PK profile of naproxen and indomethacin from plasma and urine	Day 1, Day 6 (urine only), Day 7, Day 14	Profile in terms of AUC, Tmax, Cmax, and t1/2
PK profile of lesinurad from plasma and urine	Day 1, Day 6 (urine only), Day 7, Day 14	Profile in terms of AUC, Tmax, Cmax, and t1/2 AUC: area under the plasma concentration versus time curve; Tmax: time to maximum plasma concentration; Cmax: maximum plasma drug concentration; t1/2: apparent terminal half-life

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	13 weeks