Epilepsy, Generalized Tonic-clonic Seizures
Conditions
Keywords
Levetiracetam, Epilepsy, Generalized tonic-clonic seizures
Brief summary
To evaluate the efficacy and safety of Levetiracetam dry syrup at doses up to 60 mg/kg/day or 3000 mg/day used as adjunctive therapy in Japanese pediatric patients aged ≥4 to \<16 years with uncontrolled Generalized Tonic-Clonic (GTC) seizures despite treatment with 1 or 2 Anti-Epileptic Drugs (AEDs).
Interventions
DRUGLevetiracetam
The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Sponsors
UCB Japan Co. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* An epileptic patient with generalized tonic-clonic seizures that are classifiable according to the International League Against Epilepsy classification of epileptic seizures (Epilepsia, 1981) * A patient on a stable dose of 1 or 2 anti-epileptic drugs for the last 4 weeks (potassium bromide and sodium bromide for the last 12 weeks) prior to the Combined Baseline Period and during the Combined Baseline Period
Exclusion criteria
* Presence of any sign (clinical or imaging procedures) suggesting a progressive brain lesion/disease, in particular, progressive disorder with epileptic seizures * Diagnosis of Lennox-Gastaut Syndrome * Confirmed focal epilepsy based on clinical signs (seizure types), with consistent electroencephalogram and magnetic resonance imaging features * A history of convulsive or nonconvulsive status epilepticus while taking concomitant anti-epileptic drugs for the last 3 months prior to Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent Change From the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 24-week Treatment Period (Up-Titration and Evaluation Periods) | From Baseline (Week -8) to Treatment Period (Week 0 to Week 24) | The percent change from Combined Baseline over Treatment Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Treatment Period (T) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - T)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period | From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24) | The percent change from Combined Baseline over Evaluation Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Evaluation Period (E) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - E)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7 |
| Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period | From Baseline (Week -8) to Treatment Period (Week 0 to Week 24) | The 50 % responder rate during the Treatment Period was the proportion of subjects who reported a ≥ 50 % reduction in seizure frequency per week from Baseline during the Treatment Period. |
| Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period | From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24) | The 50 % responder rate during the Evaluation Period was the proportion of subjects who reported a ≥50 % reduction in seizure frequency per week from Baseline during the Evaluation Period. |
| Generalized Tonic-clonic Seizure Freedom Over the Treatment Period | Treatment Period (Week 0 to Week 24) | A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Treatment Period was considered a seizure-free subject for that period. |
| Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period | Evaluation Period (Week 4 to Week 24) | A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Evaluation Period was considered a seizure-free subject for that period. |
Countries
Japan
Participant flow
Recruitment details
This multicenter study started to enroll subjects in Februray 2011 in order to end up with 8 sites in Japan with enrolled subjects. Participant Flow refers to the Enrolled Set (ES). ES consists of all subjects who signed the consent form and participated in the Prospective Baseline Period.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Twice daily (morning and evening) orally
Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Further treatment determined | 1 |
Baseline characteristics
| Characteristic | Levetiracetam |
|---|---|
| Age, Continuous | 9.7 years STANDARD_DEVIATION 4.1 |
| Age, Customized ≥12 to <16 years | 7 participants |
| Age, Customized ≥4 to <8 years | 4 participants |
| Age, Customized ≥8 to <12 years | 2 participants |
| Body Mass Index | 17.89 kilogram per squaremeter (kg/m^2) STANDARD_DEVIATION 3.75 |
| Height | 129.36 centimeter STANDARD_DEVIATION 26.32 |
| Region of Enrollment Japan | 13 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 9 Participants |
| Weight | 32.22 kilogram STANDARD_DEVIATION 16.56 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
The Percent Change From the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 24-week Treatment Period (Up-Titration and Evaluation Periods)
The percent change from Combined Baseline over Treatment Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Treatment Period (T) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - T)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
Time frame: From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | The Percent Change From the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 24-week Treatment Period (Up-Titration and Evaluation Periods) | 45.47 percent change | Standard Deviation 50.34 |
Secondary
Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period
A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Evaluation Period was considered a seizure-free subject for that period.
Time frame: Evaluation Period (Week 4 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.~One subject discontinued the study during the Up-Titration Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period | 2 participants |
Secondary
Generalized Tonic-clonic Seizure Freedom Over the Treatment Period
A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Treatment Period was considered a seizure-free subject for that period.
Time frame: Treatment Period (Week 0 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Generalized Tonic-clonic Seizure Freedom Over the Treatment Period | 2 participants |
Secondary
Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period
The 50 % responder rate during the Evaluation Period was the proportion of subjects who reported a ≥50 % reduction in seizure frequency per week from Baseline during the Evaluation Period.
Time frame: From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.~One subject discontinued the study during the Up-Titration Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period | 58.3 percentage of participants |
Secondary
Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period
The 50 % responder rate during the Treatment Period was the proportion of subjects who reported a ≥ 50 % reduction in seizure frequency per week from Baseline during the Treatment Period.
Time frame: From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period | 53.8 percentage of participants |
Secondary
The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period
The percent change from Combined Baseline over Evaluation Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Evaluation Period (E) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - E)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
Time frame: From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with combined Baseline Period and post-Baseline generalized tonic-clonic seizure counts. 12 of the 13 subjects in the FAS were included in the analysis excluding 1 subject discontinued before the Evaluation Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period | 44.93 percent change | Standard Deviation 51.86 |