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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Multiple 15-minute intravenous infusions of 1500 mg levetiracetam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, Japanese, Caucasian