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
Overview
- Phase
- Phase 1
- Intervention
- lesinurad 400 mg
- Conditions
- Gout
- Sponsor
- Ardea Biosciences, Inc.
- Enrollment
- 24
- Primary Endpoint
- PK profile of naproxen and indomethacin from plasma and urine
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has a body weight ≥ 50 kg (110 lbs) and a body mass index (BMI) ≥ 18 and ≤ 30 kg/m
- •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
- •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.
Arms & Interventions
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.
Intervention: lesinurad 400 mg
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.
Intervention: naproxen 250 mg
Lesinurad 400 mg and indomethacin 25 mg
Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14.
Intervention: lesinurad 400 mg
Lesinurad 400 mg and indomethacin 25 mg
Lesinurad qd Day 1, indomethacin bid Day 2-6, lesinurad qd with indomethacin bid Day 7-14.
Intervention: indomethacin 25 mg
Outcomes
Primary Outcomes
PK profile of naproxen and indomethacin from plasma and urine
Time Frame: 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
Time Frame: 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 Outcomes
- Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters(13 weeks)