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 1 month to 4 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 (1 month to 4 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 solution prior to entering the study, the levetiracetam intravenous (LEV IV) dose will be equivalent (mg-for-mg) to their oral dose (always in twice daily regimen) within the following dose range, calculated on the basis of their age and weight: * Children ≥ 1 month to \< 6 months: 14 mg/kg/day (i.e. 7 mg/kg twice daily) to 42 mg/kg/day (i.e 21 mg/kg/day twice daily); * Children ≥ 6 months to \< 4 years:20 mg/kg/day (i.e. 10 mg/kg twice daily) to 60 mg/kg/day (i.e 30 mg/kg/day twice daily). The first intravenous (IV) infusion was to be administered 12 hours after the last oral dose of levetiracetam. For children not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dose will correspond to their age and weight as follows: * Children ≥ 1 month to \< 6 months: 14 mg/kg/day (i.e. 7 mg/kg twice daily). * Children ≥ 6 months to \< 4 years: 20 mg/kg/day (i.e. 10 mg/kg 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 intravenous (LEV 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 within the following dose range, calculated on the basis of their age and weight:. * Ages ≥ 1 month to \< 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily); * Ages ≥ 6 months to \< 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: * Ages ≥ 1 month to \< 6 months: 14 mg/kg/day (7 mg/kg twice daily). * Ages ≥ 6 months to \< 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Sponsors
UCB Pharma SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 4 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 1 month and 4 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 Screening * The subject is on felbamate with less than 18 months continuous exposure before Screening. * The subject presents with current depressive symptoms, current suicidal ideation and/or behavior.
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 28 mg/kg/Day for Subjects <6 Months; >40mg/kg/Day for Subjects ≥6 Months) 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 May 2008 and continued until March 2010, with the last subject's visit occurring in March of 2010.
Pre-assignment details
Participant Flow refers to the Intent-to-treat (ITT) Population, consisting of all subjects who received at least 1 dose of study medication.
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 within the following dose range, calculated on the basis of their age and weight:.
* Ages ≥ 1 month to \< 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);
* Ages ≥ 6 months to \< 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily).
For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows:
* Ages ≥ 1 month to \< 6 months: 14 mg/kg/day (7 mg/kg twice daily).
* Ages ≥ 6 months to \< 4 years: 20 mg/kg/day (10 mg/kg twice daily). | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other: IV dose needed to be changed | 1 |
| Overall Study | Other: Unable to obtain IV & PK samples | 1 |
Baseline characteristics
| Characteristic | Levetiracetam |
|---|---|
| Age, Categorical <=18 years | 19 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 1.59 years STANDARD_DEVIATION 1.24 |
| Region of Enrollment Belgium | 1 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Mexico | 8 participants |
| Region of Enrollment Turkey | 2 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 19 |
| serious Total, serious adverse events | 4 / 19 |
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 19 subjects enrolled in the study were included 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) | 12 Subjects |
Secondary
Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received
Time frame: Treatment period (up to 4 days)
Population: All 19 subjects enrolled in the study were included 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 | 2.89 Consecutive doses | Standard Deviation 1.41 |
Secondary
Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 28 mg/kg/Day for Subjects <6 Months; >40mg/kg/Day for Subjects ≥6 Months) During the Treatment Period (up to 4 Days)
Time frame: Treatment period (up to 4 days)
Population: All 19 subjects enrolled in the study were included 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 28 mg/kg/Day for Subjects <6 Months; >40mg/kg/Day for Subjects ≥6 Months) During the Treatment Period (up to 4 Days) | 6 Subjects |