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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01618903
First received: June 11, 2012
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Human Volunteers
Drug: Levetiracetam
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

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)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  • Area under the plasma drug concentration-time curve from 0 to infinity (AUC) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
    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)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  • Plasma concentration at the end of the 45-minutes intravenous (iv) infusion (C45'(iv)) [ Time Frame: Pharmacokinetic samples were taken at 45 min after Levetiracetam administration ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  • Terminal half-life of Levetiracetam (t1/2) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
    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)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

    The CL(iv) is calculated as:

    CL=Dose of LEV/AUC.


  • Apparent total body clearance after oral administration of Levetiracetam (CL/F(tablet)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

    The CL/F (tablet) is calculated as:

    CL/F=Dose of LEV/AUC.


  • Volume of distribution after intravenous infusion of Levetiracetam (Vz(iv)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

    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)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

    The apparent volume of distribution after oral administration is calculated as:

    Vz/F= (CL/F)/λ_z.



Enrollment: 24
Study Start Date: May 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Keppra

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01618903

Locations
China
1
Shanghai, China
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01618903     History of Changes
Other Study ID Numbers: N01362A
Study First Received: June 11, 2012
Last Updated: August 2, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by UCB, Inc.:
Keppra Levetiracetam intravenous
Oral tablets
Bioequivalence
Pharmacokinetics
Safety
Chinese healthy volunteers

Additional relevant MeSH terms:
Etiracetam
Piracetam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 21, 2014