NSAID Drug Interaction Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Gout

Intervention / Treatment
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* Drug: lesinurad 400 mg
* Drug: naproxen 250 mg
* Drug: indomethacin 25 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lesinurad 400 mg and naproxen 250 mg<br>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<br> <br> Drug: naproxen 250 mg<br> <br> |
| Active Comparator: Lesinurad 400 mg and indomethacin 25 mg<br>Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14. | Drug: lesinurad 400 mg<br> <br> Drug: indomethacin 25 mg<br> <br> |

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters |  | 13 weeks |