Metformin and Furosemide Drug-Drug Interaction Study

Study Overview
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Brief Summary
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This study will assess the potential effects of lesinurad on the pharmacokinetics (PK) of metformin and furosemide in healthy, adult male subjects.

Detailed Description
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Leinurad is a weak in vitro inhibitor of the hepatic transporter OCT1 and the renal transporters OAT1 and OAT3 (OAT1/3). To assess the clinical relevance of these in vitro findings, this clinical study will evaluate the effect of lesinurad on the PK of metformin (OCT1 substrate) and furosemide (OAT1/3 substrate).

Official Title
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A Phase 1, Randomized, Open-Label, Single-Dose Study to Evaluate Potential Pharmacokinetic Interaction Between Lesinurad and Metformin and Between Lesinurad and Furosemide in Health Adult Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lesinurad 400 mg
* Drug: Metformin 850 mg
* Drug: Furosemide 40 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 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, prostatic hyperplasia, or urinary stricture. 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 Metformin<br>Sequence A- Day 1: Metformin 850 mg; Day 5: Lesinurad 400 mg with metformin 850 mg Sequence B- Day 1: Lesinurad 400 mg with metformin 850 mg; Day 5: Metformin 850 mg | Drug: Lesinurad 400 mg<br> <br> Drug: Metformin 850 mg<br> <br> |
| Experimental: Lesinurad and Furosemide<br>Sequence C - Day 1: Furosemide 40 mg; Day 5: Lesinurad 400 mg with furosemide 40 mg Sequence D - Day 1: Lesinurad 400 mg with furosemide 40 mg; Day 5: Furosemide 40 mg | Drug: Lesinurad 400 mg<br> <br> Drug: Furosemide 40 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile of metformin and furosemide from plasma | Profile in terms of maximum observed concentration (Cmax), time of occurence of maximum observed concentration (Tmax), area under the concentration-time curve (AUC), and apparent terminal half-life (t1/2). | Day 1 and Day 5 | 
| PK profile of furosemide from urine | Profile in terms of renal clearance (CLr) and amount of compound excreted into urine unchanged (Ae). | Day 1 and Day 5 | 

Secondary Outcome Measures

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