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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Volunteers
• Intervention / Treatment: Drug: Levetiracetam; Drug: Levetiracetam

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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; Drug: Levetiracetam; Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet.; Other Names: Keppra
EXPERIMENTAL: Levetiracetam oral tablet; Levetiracetam oral tablet 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; Drug: Levetiracetam; Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet.; Other Names: Keppra

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: June 11, 2012
• First Submitted That Met QC Criteria: June 11, 2012
• First Posted (ESTIMATE): June 13, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 3, 2012
• Last Update Submitted That Met QC Criteria: August 2, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Bioequivalence; Keppra Levetiracetam intravenous; Oral tablets; Chinese healthy volunteers
• Additional Relevant MeSH Terms: Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: N01362A