Epilepsy, Partial
Conditions
Keywords
Epilepsy, Partial Onset Seizures, Keppra, Levetiracetam
Brief summary
Community based study assessing safety and efficacy of levetiracetam in partial onset seizures. The optimal dose in daily clinical practice will be used.
Interventions
DRUGLevetiracetam
* Pharmaceutical form: oral tablets * Concentration: 500 mg * Route of administration: Oral use
Sponsors
UCB Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with epilepsy experiencing partial seizures, whether or not secondarily generalized. * Subjects must present between 3 and 42 partial seizures over the three months prior to protocol Visit 1. * Use of one (1), but no more than two (2) concomitant marketed antiepileptic drugs (AEDs) at the time of trial entry.
Exclusion criteria
* Subjects on vigabatrin, whose visual field has not been assessed as per recommendation of the manufacturer, i.e. every 6 months. * Presence of known pseudoseizures within the last year. * Presence of progressive cerebral disease, any other progressively degenerative neurological disease, or any cerebral tumors. * Uncountable seizures (clusters) or history of convulsive status epilepticus within the last five years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events (AEs) | From Baseline until Safety visit (two weeks after last dose; up to Week 18) | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Historical Baseline in Total (Type I+II+III) Seizure Frequency Per Week Over the Treatment Period | Week 16, compared to Baseline | Percentage change from baseline in total (type I+II+III) seizure frequency over the treatment period standardized to 1 week period. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in total (type I+II+III) seizure frequency from historical baseline. |
| Percentage of Participants With 50% Response in Seizure Frequency Per Week at Week 16 | Week 16, compared to Baseline | 50% response in seizure frequency per Week is defined as \>=50% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. |
| Percentage Change From Historical Baseline in Partial (Type I) Seizure Frequency Per Week Over the Treatment Period | Week 16, compared to Baseline | Percentage change from baseline in partial (Type I) seizure frequency over the treatment period standardized to 1 week period. Type I Partial (focal, local) seizure frequency per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in partial (type I) seizure frequency from historical baseline. |
| Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Baseline, Week 16 | The overall change in the severity of the subject's illness, compared to the subject's condition prior to the levetiracetam intake, was assessed by the Investigator using Investigator's Global Evaluation Scale (IGS). Categories are as following: Marked improvement; Moderate improvement; Slight improvement; No change; Slight worsening; Moderate worsening; Marked worsening. |
| Retention Rate at Week 16 | Week 16 | Retention rate, defined as the number of subjects who were still on levetiracetam at Visit 5 (Week 16) or on the day before divided by the number of subjects in the ITT population. |
| Percentage of Participants With 100% Response in Seizure Frequency Per Week at Week 16 | Week 16, compared to Baseline | 100% response in seizure frequency per Week is defined as 100% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. |
Countries
Hong Kong, Malaysia, Philippines, Singapore, Taiwan, Thailand
Participant flow
Recruitment details
The study started to enroll patients in November 2003 and concluded in May 2006.
Pre-assignment details
Participant Flow refers to the Intend-to-treat (ITT) Set.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Subjects received open-label Levetiracetam. | 251 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Intake of expired drug | 7 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Met exclusion criteria | 1 |
| Overall Study | Patient decision | 1 |
| Overall Study | Patient met exclusion criteria | 1 |
| Overall Study | Poor compliance, dilantin toxicity | 1 |
| Overall Study | Psychological trauma | 1 |
| Overall Study | Sponsor decision | 1 |
Baseline characteristics
| Characteristic | Levetiracetam |
|---|---|
| Age, Categorical <=18 years | 10 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 240 Participants |
| Age, Continuous | 34.42 years STANDARD_DEVIATION 11.21 |
| Sex: Female, Male Female | 137 Participants |
| Sex: Female, Male Male | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 136 / 251 |
| serious Total, serious adverse events | 15 / 251 |
Outcome results
Primary
Number of Patients With Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time frame: From Baseline until Safety visit (two weeks after last dose; up to Week 18)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Number of Patients With Adverse Events (AEs) | 184 Participants |
Secondary
Percentage Change From Historical Baseline in Partial (Type I) Seizure Frequency Per Week Over the Treatment Period
Percentage change from baseline in partial (Type I) seizure frequency over the treatment period standardized to 1 week period. Type I Partial (focal, local) seizure frequency per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in partial (type I) seizure frequency from historical baseline.
Time frame: Week 16, compared to Baseline
Population: Only subjects with partial (Type I) seizure frequency per week at baseline \>= 0 and non-missing values on treatment period are included in the analysis.~Subjects withdrawing from the study are included up to their early discontinuation visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam | Percentage Change From Historical Baseline in Partial (Type I) Seizure Frequency Per Week Over the Treatment Period | -48.34 percentage changes |
Secondary
Percentage Change From Historical Baseline in Total (Type I+II+III) Seizure Frequency Per Week Over the Treatment Period
Percentage change from baseline in total (type I+II+III) seizure frequency over the treatment period standardized to 1 week period. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in total (type I+II+III) seizure frequency from historical baseline.
Time frame: Week 16, compared to Baseline
Population: Only subjects with total (Type I+II+III) seizure frequency per week at baseline \>= 0 and non-missing values on treatment period are included in the analysis.~Subjects withdrawing from the study are included up to their early discontinuation visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam | Percentage Change From Historical Baseline in Total (Type I+II+III) Seizure Frequency Per Week Over the Treatment Period | -46.43 percentage changes |
Secondary
Percentage of Participants With 100% Response in Seizure Frequency Per Week at Week 16
100% response in seizure frequency per Week is defined as 100% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period.
Time frame: Week 16, compared to Baseline
Population: Only subjects with seizure frequency per week at baseline \>= 0 and non-missing values on treatment period are taken into account for the responder rates. By convention, subjects with frequency per week at baseline equal to zero were considered as non-responder.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Percentage of Participants With 100% Response in Seizure Frequency Per Week at Week 16 | Partial (Type I) seizures | 20.2 percentage of participants |
| Levetiracetam | Percentage of Participants With 100% Response in Seizure Frequency Per Week at Week 16 | Total (type I+II+III) seizures | 20.2 percentage of participants |
Secondary
Percentage of Participants With 50% Response in Seizure Frequency Per Week at Week 16
50% response in seizure frequency per Week is defined as \>=50% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period.
Time frame: Week 16, compared to Baseline
Population: Only subjects with seizure frequency per week at baseline \>= 0 and non-missing values on treatment period are taken into account for the responder rates. By convention, subjects with frequency per week at baseline equal to zero were considered as non-responder.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Percentage of Participants With 50% Response in Seizure Frequency Per Week at Week 16 | Partial (Type I) seizures | 47.7 percentage of participants |
| Levetiracetam | Percentage of Participants With 50% Response in Seizure Frequency Per Week at Week 16 | Total (type I+II+III) seizures | 48.1 percentage of participants |
Secondary
Percentage of Patients With Categorized Change From Baseline in Severity of Illness
The overall change in the severity of the subject's illness, compared to the subject's condition prior to the levetiracetam intake, was assessed by the Investigator using Investigator's Global Evaluation Scale (IGS). Categories are as following: Marked improvement; Moderate improvement; Slight improvement; No change; Slight worsening; Moderate worsening; Marked worsening.
Time frame: Baseline, Week 16
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Slight worsening | 3.2 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Moderate worsening | 2.8 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Marked worsening | 0.4 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Marked improvement | 34.1 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Moderate improvement | 25.3 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | Slight improvement | 16.5 percentage of participants |
| Levetiracetam | Percentage of Patients With Categorized Change From Baseline in Severity of Illness | No change | 17.7 percentage of participants |
Secondary
Retention Rate at Week 16
Retention rate, defined as the number of subjects who were still on levetiracetam at Visit 5 (Week 16) or on the day before divided by the number of subjects in the ITT population.
Time frame: Week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Retention Rate at Week 16 | 85.3 percentage of participants |