An Open-label, Bioequivalence Study to Evaluate LEV Administered as a 45-min Intravenous Infusion and Same Dosage LEV Oral Tablet in Chinese

Study Overview
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Brief Summary
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The part A of N01362 is to evaluate the bioequivalence of Levetiracetam (LEV) 1500 mg intravenous (iv) infusion when compared to tablet oral administration 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 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
* Drug: Levetiracetam


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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam iv infusion<br>Levetiracetam intravenous (iv) 45 min infusion administered as one single dose. | 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 in the morning of Day 1.<br>* Other names: Keppra;|
| Experimental: Levetiracetam oral tablet<br>Levetiracetam oral tablet administered as one single dose. | Drug: Levetiracetam<br>* Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet.<br>* Other names: Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration versus time curve from hour 0 to the time with a last quantifiable concentration (AUC(0-t)) |  | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| Area under the plasma drug concentration-time curve from 0 to infinity (AUC) | The area under the curve extrapolated to infinity is calculated as the sum of AUC(0-t) and a residual part extrapolated to infinite time. | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| 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 from pre-dose to 36 hours after Levetiracetam administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration-time curve calculated from 0 to 12 h (AUC(0-12)) |  | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| 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 at 45 min after Levetiracetam administration | 
| Time to reach the maximum plasma concentration of Levetiracetam after administration (tmax) |  | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| Terminal half-life of Levetiracetam (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 from pre-dose to 36 hours after Levetiracetam administration | 
| Total body clearance after intravenous infusion of Levetiracetam (CL(iv)) | The CL(iv) is calculated as: CL=Dose of LEV/AUC. | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| Apparent total body clearance after oral administration of Levetiracetam (CL/F(tablet)) | The CL/F (tablet) is calculated as: CL/F=Dose of LEV/AUC. | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| Volume of distribution after intravenous infusion of Levetiracetam (Vz(iv)) | The volume of distribution after iv infusion is calculated as: Vz=CL/λ_z, where CL is the total body clearance and λ_z the first order rate constant of elimination. | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 
| Apparent volume of distribution after oral administration of Levetiracetam (Vz/F(tablet)) | The apparent volume of distribution after oral administration is calculated as: Vz/F= (CL/F)/λ_z. | Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration | 

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