Epilepsy
Conditions
Keywords
levetiracetam, topiramate, epilepsy, partial seizures
Brief summary
To assess the long-term effects of levetiracetam on retention rate in subjects with refractory partial onset seizure that are not fully controlled with 1 to 3 concomitant antiepileptic drugs, compared to topiramate as add-on therapy during 52 weeks.
Interventions
DRUGLevetiracetam
250 mg and 500 mg levetiracetam tablet 1000 mg/day (500 mg bid) levetiracetam (maximum to 3000 mg/day) Duration: maximum 52 weeks
DRUGTopiramate
25 mg and 100 mg topiramate tablet 100 mg/day(50 mg bid) topiramate (maximum to 400 mg/day) Duration: maximum 52 weeks
Sponsors
UCB Korea Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects from 16 to 80 years, inclusive. Subjects under 20 years may only be included where legally permitted and ethically accepted * Subjects with refractory epilepsy with partial onset seizure classifiable according to the International League Against Epilepsy (ILAE). * Subjects having at least 2 partial onset seizures whether or not secondarily generalized during the 8 weeks historical baseline preceding V1 according to ILAE classification * Subjects having at least 1 partial onset seizures whether or not secondarily generalized per 4 weeks preceding V2 according to ILAE classification * Subjects with each interval of partial onset seizures less than 6 weeks during entire 12 weeks (8 weeks preceding V1 and 4 weeks preceding V2) * Subjects being uncontrolled while treated by 1 to 3 permitted concomitant AEDs. * Permitted concomitant AEDs having been stable and at optimal dosage for the subject from at least 4 week before V1 and during 4 weeks preceding V2 and expected to be kept stable during the Treatment Period.
Exclusion criteria
* Subjects presenting any generalized epilepsies classified as type II according to the ILAE classification (ref to publication from 1981) * Subjects suffering from epilepsies and syndromes undetermined whether focal or generalized (classification III according to the ILAE classification) * Subjects suffering from special syndromes (classification IV according to the ILAE classification) * History or occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before V2. * Presence of exclusively type IA non-motor seizures. * History or presence of status epilepticus within last 3 months preceding V1 or during Baseline * History or presence of known pseudo-seizures * Subjects who are currently on vigabatrin. (Subjects who received vigabatrin in the past and have a normal visual field test are allowed.) * Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: antipsychotics drugs, and psychostimulant (amphetamine derivatives)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate | From Baseline to Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52 | From Baseline to Week 52 | — |
| Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE) | From Baseline to Week 52 | — |
| Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | From Baseline to Week 52 | Reduction from baseline was defined as baseline value minus post-baseline value and therefore is the negative of the change from baseline value. |
| Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | From Baseline to Week 52 | — |
Countries
South Korea
Participant flow
Recruitment details
447 subjects were screened, 343 subjects were randomized.
Pre-assignment details
Participant Flow refers to the Randomized Set which consists of all subjects who were randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam 250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks | 177 |
| Topiramate 25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks | 166 |
| Total Title | 343 |
| Total | 686 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | AE, non-serious non-fatal | 13 | 17 |
| Overall Study | Lack of Efficacy | 8 | 8 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other Reason | 13 | 10 |
| Overall Study | Protocol Violation | 13 | 8 |
| Overall Study | SAE, non-fatal | 0 | 4 |
| Overall Study | SAE, non-fatal+AE, non-serious non-fatal | 1 | 0 |
| Overall Study | Withdrawal by Subject | 18 | 17 |
Baseline characteristics
| Characteristic | Levetiracetam | Topiramate | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical >=65 years | 8 Participants | 4 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 165 Participants | 162 Participants | 327 Participants |
| Age, Continuous | 40.9 years STANDARD_DEVIATION 13.6 | 39.7 years STANDARD_DEVIATION 11.8 | 40.3 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 71 Participants | 64 Participants | 135 Participants |
| Sex: Female, Male Male | 106 Participants | 102 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 86 / 177 | 91 / 166 |
| serious Total, serious adverse events | 10 / 177 | 15 / 166 |
Outcome results
Primary
Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate
Time frame: From Baseline to Week 52
Population: The Full Analysis Set (FAS) consisted of all subjects in the Safety Set who returned at least 1 post-baseline seizure diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Full Analysis Set) | Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate | 59.1 percentage of subjects |
| Topiramate (Full Analysis Set) | Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate | 56.6 percentage of subjects |
Comparison: The Odds Ratio (OR) for LEV vs TPM is based on logistic regression modeling of subject retention by treatment and center pooling category. A profile likelihood confidence interval for the OR is presented.p-value: =0.700795% CI: [0.7, 1.7]Regression, Logistic
Secondary
Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52
Reduction from baseline was defined as baseline value minus post-baseline value and therefore is the negative of the change from baseline value.
Time frame: From Baseline to Week 52
Population: The Full Analysis Set (FAS) consists of all subjects in the Safety Set (SS) who returned at least 1 postbaseline seizure diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam (Full Analysis Set) | Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | 74.47 percent reduction |
| Topiramate (Full Analysis Set) | Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | 67.86 percent reduction |
Secondary
Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52
Time frame: From Baseline to Week 52
Population: The Safety Set (SS) consists of all subjects who were randomized and received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Full Analysis Set) | Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52 | 125 Participants |
| Topiramate (Full Analysis Set) | Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52 | 128 Participants |
Secondary
Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52
Time frame: From Baseline to Week 52
Population: The Full Analysis Set (FAS) consists of all subjects in the SS who returned at least 1 postbaseline seizure diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Full Analysis Set) | Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | 120 responders |
| Topiramate (Full Analysis Set) | Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | 107 responders |
Secondary
Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE)
Time frame: From Baseline to Week 52
Population: The Safety Set (SS) consists of all subjects who were randomized and received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam (Full Analysis Set) | Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE) | NA month |
| Topiramate (Full Analysis Set) | Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE) | NA month |