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

Sponsor

UCB Pharma (Industry)

Overall Status

Completed

CT.gov ID

NCT01618903

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Human Volunteers	Drug: Levetiracetam Drug: Levetiracetam	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Levetiracetam iv infusion Levetiracetam intravenous (iv) 45 min infusion administered as one single dose.	Drug: Levetiracetam 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. Other Names: Keppra
Experimental: Levetiracetam oral tablet Levetiracetam oral tablet administered as one single dose.	Drug: Levetiracetam Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet. Other Names: Keppra

Arm

Intervention/Treatment

Experimental: Levetiracetam iv infusion

Levetiracetam intravenous (iv) 45 min infusion administered as one single dose.

Drug: Levetiracetam

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.

Other Names:

Keppra

Experimental: Levetiracetam oral tablet

Levetiracetam oral tablet administered as one single dose.

Drug: Levetiracetam

Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet.

Other Names:

Keppra

Outcome Measures

Primary Outcome Measures

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) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
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.
Maximum measured plasma concentration (Cmax) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
The value of the maximum plasma concentration is directly obtained from the observed plasma concentration versus time curves.

Secondary Outcome Measures

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)) [Pharmacokinetic samples were taken at 45 min after Levetiracetam administration]
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.
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) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
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.
Total body clearance after intravenous infusion of Levetiracetam (CL(iv)) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
The CL(iv) is calculated as: CL=Dose of LEV/AUC.
Apparent total body clearance after oral administration of Levetiracetam (CL/F(tablet)) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
The CL/F (tablet) is calculated as: CL/F=Dose of LEV/AUC.
Volume of distribution after intravenous infusion of Levetiracetam (Vz(iv)) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
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.
Apparent volume of distribution after oral administration of Levetiracetam (Vz/F(tablet)) [Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration]
The apparent volume of distribution after oral administration is calculated as: Vz/F= (CL/F)/λ_z.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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