Randomized, Placebo-controlled Study to Evaluate Effects of E5555 on Renal Function Parameters and OCT2 Activity

A Single-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Multiple Doses of E5555 on the Pharmacokinetics of Metformin (a Substrate for OCT2 Transporter) and on Renal Function in Healthy Subjects

This is a drug-drug interaction study to evaluate the effects of steady-state exposure of E5555 and its main metabolites on the pharmacokinetics (PK) of metformin, an organic cation transporter-2 (OCT2) substrate. In addition, the study will also investigate the effects of E5555 on several renal function parameters.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: E5555; Drug: E5555

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 661200
      • Quintiles Phase I Services

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Healthy male or female subjects aged greater than or equal to 18 years to 55 years

Exclusion Criteria:

• History of any medical condition which will result in an increased risk of bleeding including but not limited to active or recurrent gastric ulcers, recent head trauma or surgery, severe hypertension, bacterial endocarditis, etc.
• Creatinine clearance < 90 mL/min as estimated using Cockcroft-Gault formula at screening or baseline
• History of any renal disorders, proteinuria, hepato-biliary disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: E5555; Drug: Oral E5555 400 mg/matching placebo, oral metformin 500 mg, iohexal 20 mL intravenous (IV), and para-aminohippuric acid (PAH) 7 mg/kg IV.; Drug: E5555; Drug: Oral E5555 100 mg/matching placebo, oral metformin 500 mg, iohexal 20 mL intravenous (IV), and para-aminohippuric acid (PAH) 7 mg/kg IV bolus.
Experimental: Arm 2	Drug: E5555; Drug: Oral E5555 400 mg/matching placebo, oral metformin 500 mg, iohexal 20 mL intravenous (IV), and para-aminohippuric acid (PAH) 7 mg/kg IV.; Drug: E5555; Drug: Oral E5555 100 mg/matching placebo, oral metformin 500 mg, iohexal 20 mL intravenous (IV), and para-aminohippuric acid (PAH) 7 mg/kg IV bolus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effects of multiple doses of E5555 on single dose pharmacokinetics of metformin.	15 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effects of multiple doses of E5555 on the glomerular filtration rate estimated using iohexol.	Days 7 and 14
To assess the effects of multiple doses of E5555 on the effective renal plasma flow estimated using para-aminohippuric acid (PAH).	Days 7 and 14
To assess the multiple dose pharmacokinetics of E5555 and its main 6 metabolites.	Days 12-18
To assess the safety and tolerability of multiple doses of E5555 and a single dose of metformin either given alone or concomitantly	Day 1 - Day 18

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Dr. Bhaskar Rege, Eisai Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (Estimate): November 16, 2010

Study Record Updates

• Last Update Posted (Estimate): July 11, 2014
• Last Update Submitted That Met QC Criteria: July 10, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: E5555-A001-023