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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 28, 2014