Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures

NCT ID: NCT00884052

Last Updated: 2020-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2011-10-31

Brief Summary

The hypothesis is that a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg of Levetiracetam is going to be safe and effective in the treatment of seizures in neonates.

Detailed Description

In adults, drug clearance is less than half of the glomerular filtration rate and the drug half-life is 6-8 hours. Renal function in infants at birth is characterized by immature glomerular filtration and is only 20% that of older children. The specific esterase responsible for levetiracetam hydrolysis has not been identified and its expression in newborn infants is unknown. Depending on its activity, the expected infant total levetiracetam clearance will likely be between 15-45% of older populations. However, due to immaturity in levetiracetam clearance in infants, accumulation with multiple dosing is possible. Therefore the maintenance dose is reduced compared to older children according to the anticipated impaired clearance.

These anticipated differences in levetiracetam clearance and volume of distribution, will likely result in a prolonged drug half-life of 10-30 hours in infants. This prolonged elimination will require longer sampling to adequately characterize levetiracetam pharmacodynamics in this population.

The primary intent of the data analysis is to determine levetiracetam pharmacokinetics in newborn infants and predict the dosage necessary to maintain concentrations similar to those seen with effective therapy in other populations. Graphs of serum concentration vs. time will be plotted for levetiracetam for each infant. Mean serum drug concentration vs. time curves will also be constructed. Summary statistics (i.e., n, mean, standard deviation, minimum, maximum, and coefficient of variation) will be calculated for serum concentrations for each time point and each dose level.

Conditions

Seizures; Disorder of Fetus or Newborn

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

levetiracetam dose escalation

6 Babies in Phase 1-Received Dose 1: 20 mg/kg; 5 mg/kg daily 12 Babies in Phase 2-Received Dose 2: 40 mg/kg; 10 mg/kg/day

Group Type: EXPERIMENTAL

Low dose levetiracetam

Intervention Type: DRUG

20 mg/kg loading dose; 5 mg/kg daily for 7 days.

High dose levetiracetam

Intervention Type: DRUG

40 mg/kg IV load; 10 mg/kg/day maintenance

Interventions

Low dose levetiracetam

20 mg/kg loading dose; 5 mg/kg daily for 7 days.

Intervention Type: DRUG

High dose levetiracetam

40 mg/kg IV load; 10 mg/kg/day maintenance

Intervention Type: DRUG

Other Intervention Names

Keppra; Keppra

Eligibility Criteria

Inclusion Criteria

• Newborns admitted to the UCSD, Children's Hospital or Sharp Mary Birch NICUs with seizures.
• Term infants (gestational age greater than or equal to 37 weeks.
• > 2500 grams (max blood for study 6mL =3%).
• Postnatal age 14 days or less.
• Serum creatinine less than 1.2 at time of enrollment.
• Received loading dose of phenobarbital 20mg/kg.
• Are still experiencing either clinical or electroencephalographic seizures despite this therapy.
• For whom parental consent to participate in the study is obtained.

Exclusion Criteria

• Biochemical abnormality - hypoglycemia, hypocalcemia-that when treated result in seizure cessation.
• Severe hypoxic ischemic injury likely to result in imminent death
• The only significant exclusions that will be made in recruitment and enrollment will be the exclusion of infants who are judged by the attending neonatologist to be so critically ill that death is imminent and benefit from neonatal intensive care is very unlikely.
• No rule-based criteria, (using lab or clinical parameters) adequately capture the complete nature of this clinical assessment.
• In general any child receiving active treatment with head cooling will not be excluded.

• Minimum Eligible Age: 1 Minute
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

Richard H. Haas

OTHER

Sponsor Role: lead

Responsible Party

Richard H. Haas

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Richard Haas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calfornia, San Diego

Locations

University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)

San Diego, California, United States

Countries

United States

References

Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.

Reference Type: RESULT

PMID: 22495532 (View on PubMed)

Other Identifiers

Thrasher 02825-1

Identifier Type: -

Identifier Source: org_study_id

NCT00461409

Identifier Type: -

Identifier Source: nct_alias