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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01241669

Enrollment

104

Registered

2010-11-16

Start date

2010-10-31

Completion date

Unknown

Last updated

2014-07-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Subjects

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.

Interventions

DRUGE5555

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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

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.

Design outcomes

Primary

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

Secondary

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

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026