Lesinurad Interaction Study With Ranitidine

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 ranitidine on lesinurad.

Detailed Description
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This study will evaluate the potential effect of ranitidine on the pharmacokinetics of lesinurad. An earlier study demonstrated an effect on lesinurad PK in the presence of both calcium-containing and magnesium- and aluminum-containing antacids. The current study will assess whether raising gastric pH, without the presence of these cations, affects lesinurad PK and PD under the fasted state. If an impact is seen, then the optional second cohort will be conducted under the fed state.

Official Title
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A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Potential Effects of Ranitidine on the Pharmacokinetics of Lesinurad in Healthy Adult Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: lesinurad 400 mg
* Drug: ranitidine 150 mg
* Drug: lesinurad 400 mg + ranitidine 150 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m2. Screening sUA value ≤ 7.0 mg/dL. 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 abnormalties in vital signs, ECG, physical examination or safety laboratory values per the Investigator's judgment. Exclusion Criteria: history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic renal,urological, or psychiatric disorders. history or suspicion of kidney stones. undergone major surgery within 3 months prior to Day 1. 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. 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1 fasted<br>Day 1: Lesinurad 400 mg once daily (qd) Day 5: Ranitidine 150 mg twice daily (bid) Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad. Day 7: Ranitidine 150 mg (bid) | Drug: lesinurad 400 mg<br> <br> Drug: ranitidine 150 mg<br> <br> Drug: lesinurad 400 mg + ranitidine 150 mg<br> <br> |
| Experimental: Sequence 2 fasted<br>Day 1: Ranitidine 150 mg (bid) Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad Day 3: Ranitidine 150 mg (bid) Day 7: Lesinurad 400 mg (qd) | Drug: lesinurad 400 mg<br> <br> Drug: ranitidine 150 mg<br> <br> Drug: lesinurad 400 mg + ranitidine 150 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 Cmax, Tmax, AUC, CL/F, t1/2 Cmax: maximum concentration; Tmax: time to reach max plasma concentration; AUC: area under the concentration-time curve; CL/F: total body clearance corrected for bioavailability; t1/2: apparent terminal half-life | Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters |  | 6 weeks | 
| PD profile of lesinurad from serum | Profile in terms of serum urate concentration | Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2) |