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

Sponsor

Eisai Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01241669

Collaborator

(none)

104

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: E5555 Drug: E5555	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Aug 1, 2011

Arms and Interventions

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.
Experimental: Arm 2	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.

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.

Experimental: Arm 2

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.

Outcome Measures

Primary Outcome Measures

To evaluate the effects of multiple doses of E5555 on single dose pharmacokinetics of metformin. [15 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Quintiles Phase I Services	Overland Park	Kansas	United States	661200

Sponsors and Collaborators

Eisai Inc.

Investigators

Study Director: Dr. Bhaskar Rege, Eisai Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Eisai Inc.

ClinicalTrials.gov Identifier:

NCT01241669

Other Study ID Numbers:

E5555-A001-023

First Posted:

Nov 16, 2010

Last Update Posted:

Jul 11, 2014

Last Verified:

Jul 1, 2014

Study Results

No Results Posted as of Jul 11, 2014