NSAID Drug Interaction Study

A Phase 1 Study to Evaluate the Potential Two-Way Pharmacokinetic Interaction Between Lesinurad and Naproxen and Between Lesinurad and Indomethacin in Healthy Adult Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: lesinurad 400 mg; Drug: naproxen 250 mg; Drug: indomethacin 25 mg

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lesinurad 400 mg and naproxen 250 mg; Lesinurad once daily (qd) Day 1, naproxen twice daily (bid) Day 2-6, lesinurad qd with naproxen bid Day 7-14.	Drug: lesinurad 400 mg; Drug: naproxen 250 mg
Active Comparator: Lesinurad 400 mg and indomethacin 25 mg; Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14.	Drug: lesinurad 400 mg; Drug: indomethacin 25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile of lesinurad from plasma and urine	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	Day 1, Day 6 (urine only), Day 7, Day 14
PK profile of naproxen and indomethacin from plasma and urine	Profile in terms of AUC, Tmax, Cmax, and t1/2	Day 1, Day 6 (urine only), Day 7, Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	13 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: S Bradley, MD, Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 20, 2013
• First Posted (Estimate): June 24, 2013

Study Record Updates

• Last Update Posted (Estimate): November 8, 2013
• Last Update Submitted That Met QC Criteria: November 6, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Renal Agents; Uricosuric Agents; Indomethacin; Lesinurad; Naproxen
• Other Study ID Numbers: RDEA594-126