Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Information provided by (Responsible Party):
Eisai Inc. Identifier:
First received: November 15, 2010
Last updated: July 10, 2014
Last verified: July 2014

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 Intervention Phase
Healthy Subjects
Drug: E5555
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • To evaluate the effects of multiple doses of E5555 on single dose pharmacokinetics of metformin. [ Time Frame: 15 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effects of multiple doses of E5555 on the glomerular filtration rate estimated using iohexol. [ Time Frame: Days 7 and 14 ] [ Designated as safety issue: No ]
  • To assess the effects of multiple doses of E5555 on the effective renal plasma flow estimated using para-aminohippuric acid (PAH). [ Time Frame: Days 7 and 14 ] [ Designated as safety issue: No ]
  • To assess the multiple dose pharmacokinetics of E5555 and its main 6 metabolites. [ Time Frame: Days 12-18 ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of multiple doses of E5555 and a single dose of metformin either given alone or concomitantly [ Time Frame: Day 1 - Day 18 ] [ Designated as safety issue: Yes ]

Enrollment: 104
Study Start Date: October 2010
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
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Please refer to this study by its identifier: NCT01241669

United States, Kansas
Quintiles Phase I Services
Overland Park, Kansas, United States, 661200
Sponsors and Collaborators
Eisai Inc.
Study Director: Dr. Bhaskar Rege Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc. Identifier: NCT01241669     History of Changes
Other Study ID Numbers: E5555-A001-023
Study First Received: November 15, 2010
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration processed this record on February 25, 2015