Antacid Interaction Study

Study Overview
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Brief Summary
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This study will assess the potential effects of calcium carbonate and aluminum/magnesium hydroxide-containing antacids on the pharmacokinetics (PK) and pharmacodynamics (PD) of lesinurad in healthy, adult male subjects.

Detailed Description
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In this study, lesinurad and antacid will be administered in the fed state, antacid doses will be attenuated to reflect the more commonly used doses, baseline PD assessments will be performed both in presence and absence of antacid treatment, and the sequence of treatments (lesinurad +/- antacid) will be randomized.

Official Title
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A Phase 1, Randomized, Open-Label, Drug-Drug Interaction Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interaction Between Lesinurad and Calcium Carbonate and Aluminum/Magnesium Hydroxide-Containing Antacids in Healthy Adult Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lesinurad 400 mg
* Drug: Tums 500 mg and 750 mg
* Drug: MINTOX 10 mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m2. Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment Exclusion Criteria: Subject has a history or suspicion of kidney stones. Subject has undergone major surgery within 3 months prior to Screening. Subject donated blood or experienced significant blood loss (>450 mL) within 12 weeks prior to Screening or gave a plasma donation within 4 weeks prior to Screening. 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lesinurad and Tums<br>Day 1: 240 mL water or 240 mL water and Tums Day 2: Lesinurad 400 mg or Lesinurad 400 mg and Tums; Day 6: 240 mL water and Tums or 240 mL water; Day 7: Lesinurad 400 mg and Tums or Lesinurad 400 mg | Drug: Lesinurad 400 mg<br> <br> Drug: Tums 500 mg and 750 mg<br> <br> |
| Experimental: Lesinurad and MINTOX<br>Day 1: 240 mL water or 240 mL water and MINTOX ; Day 2: Lesinurad 400 mg or Lesinurad 400 mg and MINTOX; Day 6: 240 mL water and MINTOX or 240 mL water; Day 7: Lesinurad 400 mg and MINTOX or Lesinurad 400 mg | Drug: Lesinurad 400 mg<br> <br> Drug: MINTOX 10 mL<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 | Plasma in terms of maximum observed concentration (Cmax), time of occurrence of maximum observed concentration (Tmax), area under the concentration-time curve (AUC), apparent terminal half-life (t½), renal clearance (CLR), and adverse event (Ae). | Day 2 and Day 7 | 
| PD profile of Lesinurad from serum and urine | Serum PD in terms of serum urate concentration, urine uric acid excretion amount, renal clearance of uric acid, and fractional excretion of uric acid. | Day 2 and Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters |  | 5 weeks |