SeizuresPhase 1/2KeppraNCT00884052
Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
A Phase 1/2 study testing Low dose levetiracetam and High dose levetiracetam in people with Seizures and Disorder of Fetus or Newborn, run by Richard H. Haas at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 minute to 14 days
- Conditions the study is for
- Seizures, Disorder of Fetus or Newborn
- What is being tested?
- Low dose levetiracetam and High dose levetiracetam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Oct 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 minute to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
- Mechanical ventilation and/or the use of inotropic agents to support blood pressure will not be exclusion criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)
San Diego, California, 92103
About this study
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.
Read the 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
- Being tested
- Low dose levetiracetam, High dose levetiracetam
- Keywords
- Neonatal seizures
- Medical subject headings
- Seizures, Fetal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose levetiracetamDrug
Also called Keppra
20 mg/kg loading dose; 5 mg/kg daily for 7 days.
High dose levetiracetamDrug
Also called Keppra
40 mg/kg IV load; 10 mg/kg/day maintenance
| Study group | Role | What they receive |
|---|---|---|
| levetiracetam dose escalation | Experimental | 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 Receives: Drug: Low dose levetiracetam; Drug: High dose levetiracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Clearance
Measured: Day 1 and Day 7
Drug Half Life
Measured: Day 1 and Day 7
Secondary outcomes (1)
Levetiracetam Treated Number of Participants With Serious Adverse Events
Measured: 7 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2009 (estimated)
- Study startApr 2007
- Primary completionMar 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SeizuresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard H. Haas
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Sponsor-investigator, Richard H. Haas, University of California, San Diego
- Investigators
- Richard Haas, MD, Principal investigator, University of Calfornia, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00884052
- Sponsor's protocol ID
- Thrasher 02825-1
- Acronym
- Keppra
- Status last verified
- Mar 2020
- First submitted
- 17 Apr 2009
- Last updated
- 26 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22495532
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
- ClinicalTrials.gov ID
- NCT00884052
- Acronym / sponsor ID
- Keppra / Thrasher 02825-1
- Conditions
- Seizures, Disorder of Fetus or Newborn
- Keywords
- Neonatal seizures
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Richard H. HaasUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- Apr 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 20 Apr 2009 (estimated)
- Results
- Posted 26 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| levetiracetam dose escalation | Experimental | Drug: Low dose levetiracetam, Drug: High dose levetiracetam6 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 |
Who may qualify
- Ages
- 1 minute to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low dose levetiracetamAlso: Keppra20 mg/kg loading dose; 5 mg/kg daily for 7 days. | Drug | levetiracetam dose escalation |
| High dose levetiracetamAlso: Keppra40 mg/kg IV load; 10 mg/kg/day maintenance | Drug | levetiracetam dose escalation |
Primary outcome
Drug Clearance
Time frame: Day 1 and Day 7
Drug Half Life
Time frame: Day 1 and Day 7
1 secondary outcome
Levetiracetam Treated Number of Participants With Serious Adverse Events
Time frame: 7 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22495532Sharpe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Haas, MD principal investigator
University of Calfornia, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low dose levetiracetam and High dose levetiracetam in people with Seizures and Disorder of Fetus or Newborn, run by Richard H. Haas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug Clearance (time frame: Day 1 and Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00884052, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020.