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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Ardea Biosciences, Inc.
- Enrollment
- 23
- Primary Endpoint
- PK profile of metformin and furosemide from plasma
Study Overview
Brief Summary
This study will assess the potential effects of lesinurad on the pharmacokinetics (PK) of metformin and furosemide in healthy, adult male subjects.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subject has a body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m
- •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.
Arms & Interventions
Lesinurad and Metformin
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
Intervention: Lesinurad 400 mg (Drug)
Lesinurad and Metformin
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
Intervention: Metformin 850 mg (Drug)
Lesinurad and Furosemide
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
Intervention: Lesinurad 400 mg (Drug)
Lesinurad and Furosemide
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
Intervention: Furosemide 40 mg (Drug)
Outcomes
Primary Outcomes
PK profile of metformin and furosemide from plasma
Time Frame: Day 1 and Day 5
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).
PK profile of furosemide from urine
Time Frame: Day 1 and Day 5
Profile in terms of renal clearance (CLr) and amount of compound excreted into urine unchanged (Ae).
Secondary Outcomes
- Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters(5 weeks)