Epilepsy
Conditions
Keywords
Epilepsy, Child, Levetiracetam, Keppra®, Infusion, Intravenous
Brief summary
Keppra injection is approved in the US as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. The objective of the current study is to assess the safety, tolerability, and pharmacokinetics, of this formulation in children aged 4 to 16 years.
Detailed description
The primary objective of this study was to evaluate the safety and tolerability of levetiracetam intravenous 15-minute infusion administered every 12 hours, either as adjunctive treatment or monotherapy in children (4 to 16 years old) with epilepsy (except status epilepticus), either after switching from the equivalent levetiracetam oral dose administration or as a new antiepileptic treatment. The evaluation period was to be considered as one complete set of 4 Pharmacokinetic (PK) samples for a maximum of 4 days; * For children already taking levetiracetam oral tablets or oral solution prior to entering the study, the levetiracetam intravenous (LEV IV) dose will be equivalent (mg-for-mg) to their oral dose. The first intravenous (IV) infusion was to be administered 12 hours after the last oral dose of levetiracetam. * For children not taking levetiracetam oral tablets or oral solution prior to entering the study: * If weight \< 50 kg: dose of levetiracetam intravenous (LEV IV) dose will be calculated on the basis of their weight at 20 mg/kg/day (i.e. 10 mg/kg twice daily). * If weight ≥ 50 kg: dose of levetiracetam intravenous (LEV IV) will be 1000 mg/day (i.e. 500 mg twice daily). However, when necessary for the safety of the subject or when the investigator deemed it appropriate the levetiracetam intravenous (LEV IV) dose could be modified after one day. Subjects were hospitalized for the duration of the levetiracetam IV treatment.
Interventions
DRUGLevetiracetam
Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose. Dosage for subjects not on levetiracetam at study entry was based on weight: if \<50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Sponsors
UCB Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 4 and 16 years of age, inclusive * The subject suffers from epilepsy (except status epilepticus) * The subject is requiring levetiracetam IV treatment in place of oral therapy for a short period of time
Exclusion criteria
* The subject has difficult venous accessibility * History of status epilepticus during the 3 months prior to visit 1. * The subject is taking felbamate at visit 1 or has been taking it in the past.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days) | Treatment period (up to 4 days) |
Secondary
| Measure | Time frame |
|---|---|
| Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 40 mg/kg/Day) During the Treatment Period (up to 4 Days) | Treatment period (up to 4 days) |
| Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received | Treatment period (up to 4 days) |
Countries
Belgium, France, Germany, Mexico, Turkey (Türkiye), United States
Participant flow
Recruitment details
Subjects were recruited from sites in the United States, Belgium, Germany, France, Mexico, and Turkey. The study began in September 2007 and continued until February 2010, with the last subject's visit occurring in February of 2010.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Intravenous 100 mg/mL, twice a day, maximum of 4 days
Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose.
Dosage for subjects not on levetiracetam at study entry was based on weight: if \<50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily). | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | Levetiracetam |
|---|---|
| Age, Categorical <=18 years | 33 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 9.71 years STANDARD_DEVIATION 3.38 |
| Region of Enrollment Belgium | 5 participants |
| Region of Enrollment France | 4 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Mexico | 10 participants |
| Region of Enrollment Turkey | 6 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 33 |
| serious Total, serious adverse events | 3 / 33 |
Outcome results
Primary
Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days)
Time frame: Treatment period (up to 4 days)
Population: All 33 subjects enrolled in the study were in the Intent to Treat (ITT) population and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days) | 21 Subjects |
Secondary
Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received
Time frame: Treatment period (up to 4 days)
Population: All 33 subjects enrolled in the study were in the Intent to Treat (ITT) population and are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received | 3.73 Consecutive doses | Standard Deviation 1.61 |
Secondary
Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 40 mg/kg/Day) During the Treatment Period (up to 4 Days)
Time frame: Treatment period (up to 4 days)
Population: All 33 subjects enrolled in the study were in the Intent to Treat (ITT) population and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 40 mg/kg/Day) During the Treatment Period (up to 4 Days) | 10 Subjects |