Metformin and Furosemide Drug-Drug Interaction Study

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lesinurad 400 mg; Drug: Metformin 850 mg; Drug: Furosemide 40 mg

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Lesinurad 400 mg; Drug: Metformin 850 mg
Experimental: 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	Drug: Lesinurad 400 mg; Drug: Furosemide 40 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: S. Bradley, Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: January 6, 2014
• First Posted (Estimate): January 7, 2014

Study Record Updates

• Last Update Posted (Estimate): February 14, 2014
• Last Update Submitted That Met QC Criteria: February 13, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Gout Suppressants; Sodium Potassium Chloride Symporter Inhibitors; Renal Agents; Uricosuric Agents; Metformin; Furosemide; Lesinurad
• Other Study ID Numbers: RDEA594-128