Metformin and Furosemide Drug-Drug Interaction Study

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Lesinurad 400 mg; Drug: Metformin 850 mg; Drug: Furosemide 40 mg

• Registration Number: NCT02028689
• Lead Sponsor: Ardea Biosciences, Inc.

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 Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-17
• Primary Completion: 2013-11
• Study Completion: 2014-01
• Study First Submitted QC: 2014-01-06
• Study First Posted: 2014-01-07
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-13
• Last Update Posted: 2014-02-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lesinurad and Metformin	Lesinurad 400 mg	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
Lesinurad and Metformin	Metformin 850 mg	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
Lesinurad and Furosemide	Lesinurad 400 mg	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
Lesinurad and Furosemide	Furosemide 40 mg	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

Primary Outcome Measures

Name	Time	Method
PK profile of metformin and furosemide from plasma	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	Day 1 and Day 5	Profile in terms of renal clearance (CLr) and amount of compound excreted into urine unchanged (Ae).

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	5 weeks