IV Levetiracetam for the Treatment of Neonatal Seizures: a Pharmacokinetic and Preliminary Efficacy and Safety Study

Seizures Clinical Trial

Official title:

Phase I/II Study of IV Levetiracetam as an add-on Drug for Seizures in Term Neonates Assessing Pharmacokinetics, Safety and Efficacy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461409
• Other study ID #: NeoLev 1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 16, 2007
• Last updated: October 7, 2015
• Start date: April 2007
• Est. completion date: March 2011

Study information

• Verified date: October 2015
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the correct dosing for intravenous levetiracetam in term new born babies with seizures. In addition information on safety and efficacy will be collected. This new anticonvulsant drug is a promising treatment for seizures in newborns.

Description:

There is a pressing need to improve the treatment of seizures in the neonatal period. The anticonvulsant agents currently in use may damage the developing brain and are quite ineffective at controlling seizures in neonates. Newborn seizures are common (1 in 300 newborns) and are associated with very poor outcomes. 20-30% of infants with neonatal seizures die, 20-30% develop epilepsy outside the neonatal period and 20-40% develop cerebral palsy and/or mental retardation. Better treatments for neonatal seizures could improve these outcomes.

An intravenous form of the anti-seizure medication levetiracetam has been released for use in adults with epilepsy. Experience with oral levetiracetam has shown it to be a very safe medication, with good efficacy in stopping seizures in other age groups. The intravenous preparation could allow its use in neonates with seizures. Drug handling by the body is very different in neonates to adults. Before we can use levetiracetam in this age group we need to determine the correct dose and frequency by studying its absorption and distribution in the body (pharmacokinetic profile).

This study is an add-on open label pharmacokinetic and preliminary safety study. Twenty-four patients with neonatal seizures, who still experience clinical or electroencephalographic seizures after treatment with Phenobarbital will be treated with intravenous levetiracetam, and serial determinations of serum levetiracetam levels will be made to allow calculation of pharmacokinetic parameters. We will also collect preliminary safety data. We will specifically monitor for abnormalities of heart rate, respiratory rate and blood pressure, unexpected death, the occurrence of hypotonia, sedation, poor feeding, irritability or infection. Blood tests monitoring blood, liver and kidney function will be checked at baseline, 48 hours and at completion of 7 days of treatment. We will also collect preliminary descriptive data on the efficacy of levetiracetam in stopping neonatal seizures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 37 Weeks to 42 Weeks

Eligibility

Inclusion Criteria:

• Newborns admitted with seizures to the UCSD, Children's Hospital or Sharp Mary Birch NICUs in San Diego, CA, USA as well as Auckland City Hospital, Grafton,Auckland NZ :

• Term infants (gestational age greater than or equal to 37 weeks > 2460 grams (max blood for study 6mL =3%)

• Postnatal age < 14 days.

• Received loading dose of phenobarbital 20mg/kg and/or phenytoin.

• Ongoing clinical or electroencephalographic seizures despite this therapy.

• For whom parental consent to participate in the study is obtained.

Exclusion Criteria:

• Serum creatinine greater than 1.2 at enrollment or greater than 2.0 at any time.

• Biochemical abnormality - hypoglycemia, hypocalcemia- that when treated result in seizure cessation.

• Severe hypoxic ischemic injury likely to result in imminent death

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Seizures
• Term Neonates

Intervention

Drug:
• Intravenous levetiracetam
IV levetiracetam escalating to 40mg/kg load and daily 10mg/kg maintenance

Locations

Country	Name	City	State
New Zealand	Auckland City Hospital	Auckland
United States	Sharpe Mary Birch Hospital	San Diego	California
United States	UCSD Hillcrest Medical Center	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
Richard H. Haas	Pediatric Pharmacology Research Units Network, Thrasher Research Fund

Countries where clinical trial is conducted

United States,  New Zealand, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic data on intravenous levetiracetam administered to term neonates over 7 days.		Study completion	No
Secondary	Preliminary safety data and efficacy data will be collected.		Study completion	Yes