Multiple-dose Study of Levetiracetam Injection in Japanese and Caucasian Healthy Males

A Single-center, Open-label, Multiple-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Levetiracetam Administered as Intravenous Infusion in Japanese and Caucasian Healthy Male Subjects

To compare the pharmacokinetics of levetiracetam following single and multiple 15-minute intravenous infusions of 1500 mg levetiracetam between Japanese and Caucasian healthy male subjects

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Multiple 15-minute intravenous infusions of 1500 mg levetiracetam

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy Japanese and Caucasian males with the age between 20 and 40 years old,
• with the body mass index between 20 and 25,
• with the body weight between 60 and 80kg

Exclusion Criteria:

• subjects who have a history or presence of drug addiction or excessive use of alcohol
• current smokers and former smokers who have given up since less than 6 months before the first dose
• heavy caffeine drinker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam IV infusions in Japanese; Multiple 15-minute intravenous infusions of 1500 mg levetiracetam in Japanese subjects	Drug: Multiple 15-minute intravenous infusions of 1500 mg levetiracetam; Strength, 100 mg/mL; Form, concentrate for solution for infusion; Frequency, twice a day; Duration, 7 days; Other Names: E-Keppra
Experimental: Levetiracetam IV infusions in Caucasian; Multiple 15-minute intravenous infusions of 1500 mg levetiracetam in Caucasian subjects	Drug: Multiple 15-minute intravenous infusions of 1500 mg levetiracetam; Strength, 100 mg/mL; Form, concentrate for solution for infusion; Frequency, twice a day; Duration, 7 days; Other Names: E-Keppra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration after a single dose (Cmax)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of Intravenous (IV) infusion
Area under the curve from zero to the time of the last quantifiable concentration after a single (AUC(0-t))	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion
Area under the plasma concentration time curve from zero to infinity after a single dose (AUC)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion
Body-weight normalized maximum plasma concentration after a single dose (Cmax)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion
Body-weight normalized area under the curve from zero to the time of the last quantifiable concentration after a single, (AUC(0-t))	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion
Body weight normalized area under the plasma concentration time curve from zero to infinity after a single dose, (AUC)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion
Maximum plasma concentration at steady state after multiple doses (Cmax,ss)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.
Area under the curve over a dosing interval at steady state after multiple doses (AUCτss)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.
Body-weight normalized maximum plasma concentration at steady state after multiple doses (Cmax,ss)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.
Body-weight normalized area under the curve over a dosing interval at steady state after multiple doses (AUCτss)	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve over a dosing interval, (AUCτ (τ = 12 hours))		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion
Time to maximum plasma concentration after a single dose (tmax)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
Terminal elimination half-life after a single dose (t1/2)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
First order terminal elimination rate constant after a single dose (λz)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
Total body clearance after a single dose (CL)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
Volume of distribution during terminal phase after a single dose (Vz)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
Mean residence time after a single dose (MRT)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of IV infusion.
Time to maximum plasma concentration at steady state after multiple doses (tmax,ss)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.
Total body clearance at steady state after multiple doses (CLss)		Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of IV infusion.
Linearity factor after multiple doses (LF)	LF = AUCτss / AUC	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9, 12, 24 and 36 hours after the start of the first IV infusion and at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of the last IV infusion.
Accumulation ratio (RAUC) after multiple doses	RAUC = AUCτss / AUCτ	Multiple samples at predose, 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 6, 9 and 12 hours after the start of the first and the last IV infusions

Collaborators and Investigators

• Sponsor: UCB Japan Co. Ltd.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimate): November 12, 2012

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 27, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Healthy volunteers; Japanese; Caucasian
• Additional Relevant MeSH Terms: Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: EP0038