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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241669
• Other study ID #: E5555-A001-023
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2010
• Last updated: July 10, 2014
• Start date: October 2010

Study information

• Verified date: July 2014
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Quintiles Phase I Services	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effects of multiple doses of E5555 on single dose pharmacokinetics of metformin.		15 days	No
Secondary	To assess the effects of multiple doses of E5555 on the glomerular filtration rate estimated using iohexol.		Days 7 and 14	No
Secondary	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	No
Secondary	To assess the multiple dose pharmacokinetics of E5555 and its main 6 metabolites.		Days 12-18	No
Secondary	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	Yes