A Randomized, Double-blind, Pharmacokinetics Study to Assess Safety, Tolerability of Levetiracetam 45 Minutes Intravenous Infusion During 4 Days of Bid Dosing in Chinese Healthy Volunteers

Study Overview
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Brief Summary
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The part B of N01362 is to assess the pharmacokinetic profile of Levetiracetam 1500 mg intravenous (iv) infusion during repeated dosing in Chinese healthy volunteers.

Detailed Description
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The study includes 2 parts, part A is to evaluate the bioequivalence of Levetiracetam (LEV) 1500 mg intravenous (iv) infusion when compared to oral tablet, part B is to assess the pharmacokinetic profile of LEV infusion during repeated dosing in Chinese healthy volunteers.

Official Title
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A Monocenter, Open-label, Two-way Randomized Cross-over Study to Evaluate the Bioequivalence of Levetiracetam Administered as a 45 Minutes Intravenous Infusion and Same Dosage Levetiracetam Oral Tablet (Part A); and a Randomized, Double-blind, Placebo-controlled, Parallel Study on the Safety, Tolerability and Pharmacokinetics of Levetiracetam 45 Minutes Intravenous Infusion During 4 Days of b.i.d. Dosing (Part B), in Chinese Healthy Volunteers

Conditions
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Human Volunteers

Intervention / Treatment
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* Drug: Levetiracetam
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese, age 18-40, weight ≥ 50 kg Healthy volunteers with normal vital signs, good physical and mental health status and normal electrocardiogram and laboratory test Exclusion Criteria: History or presence of each systems disorders capable of altering the absorption, metabolism or elimination of drugs, or of constituting a risk factor when taking the study medication History or presence of drug addiction or excessive use of alcohol Symptomatic or asymptomatic Orthostatic Hypotension at screening Current smokers and former smokers Heavy caffeine drinker History of frequent and severe headache Any drug treatment Subjects who are known to have Serum Hepatitis or who are carriers of the Hepatitis B surface antigen, or Hepatitis C antibody or who are HIV positive Subjects on a controlled sodium diet Subject has made a blood donation or had a comparable blood loss

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam iv infusion<br>Levetiracetam intravenous (iv) infusion. | Drug: Levetiracetam<br>* Levetiracetam 1.500 mg (500 mg/ 5 mL vials) administered as a 45 minutes intravenous infusion diluted in 100 mL 0.9 % saline solution every 12 hours from the morning of Day 3 (it is the first day in Part B) to the morning of Day 7 (it is the 5th day in Part B).<br>* Other names: Keppra;|
| Placebo Comparator: Placebo infusion<br> | Other: Placebo<br>* 15 mL 0.9 % saline solution added to 100 mL 0.9 % saline solution, administered as a 45 minutes intravenous infusion every 12 hours from the morning of Day 3 ( it is the 1st day in Part B) to the morning of Day 7 (it is the 5th day in Part B).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration-time curve over a dosing interval (AUCτ) | The AUCτ is the area under the plasma concentration, after the last intravenous (iv) dose, versus time curve observed during the dosing interval τ. | Pharmacokinetic samples were taken 36 hours after iv administration on Day 7 | 
| Maximum measured plasma concentration (Cmax) | The value of the maximum plasma concentration is directly obtained from the observed plasma concentration versus time curves. | Pharmacokinetic samples were taken 36 hours after iv administration on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration at the end of the 45-minutes intravenous (iv) infusion (C45'(iv)) | The value of the plasma concentration at the end of the 45-min iv infusion is directly obtained from the experimental data of plasma concentration versus time curves. | Pharmacokinetic samples were taken 36 hours after iv administration on Day 7 | 
| Minimum plasma concentration over dosing interval after intravenous (iv) infusion (Cmin) |  | Pharmacokinetic samples were taken 36 hours after iv administration on Day 7 | 
| Terminal half-life (t1/2) | The terminal half-life associated with the terminal rate constant λ_z is calculated as: ln2/λ_z. λ_z is the first order rate constant of elimination. | Pharmacokinetic samples were taken 36 hours after iv administration on Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keppra Levetiracetam intravenous, Multiple dose, Safety, Pharmacokinetics, Chinese healthy volunteers