Epilepsy
Conditions
Keywords
Levetiracetam, Oxcarbazepine, treatment failure, partial epilepsy
Brief summary
To evaluate the long term effectiveness of Levetiracetam (LEV) monotherapy on Treatment Failure Rate in subjects with newly diagnosed partial onset seizures with or without secondary generalized seizures, compared to Oxcarbazepine (OXC) monotherapy over 50 weeks from the first dose
Detailed description
The study duration consists of the following periods: * Baseline period of one week: Week -1 * Titration period of two weeks: Week 0 to Week 1 * Treatment period of 48 weeks: Week 2 to Week 50
Interventions
DRUGLevetiracetam
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
DRUGOxcarbazepine
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1week then 600 mg/day 1 week)
Sponsors
Korea UCB 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. Vulnerable subjects (e.g., under 20 years or subject with learning disability but judged to be capable to understand) may only be included where legally permitted and ethically accepted * Subjects with newly or recently diagnosed epilepsy having experienced unprovoked partial seizures (IA, IB, IC with clear focal origin), that are classifiable according to the International Classification of Epileptic seizure (1981). Undiscriminated subjects between IC and IIE could be included * Subjects with at least 2 unprovoked seizures separated by a minimum of 48 hours in the year preceding randomization out of which at least 1 unprovoked seizure in the 6 months preceding randomization * Subjects with documented evidence of EEG and brain MRI or CT scan in medical records which were performed within 1 year prior to Visit 1 (V1) * Subjects have no treatment with anti-epileptic drugs in the 6 months preceding this study. The treatment for acute seizure control is acceptable with a maximum of 2 weeks duration and if the treatment was stopped at least 1 week before V1. For Phenobarbital and Phenobarbital derivatives, a minimum of 4 weeks wash-out is requested before V1
Exclusion criteria
* Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events which could be confused with seizures * Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: neuroleptics, monoamine oxidase (MAO) inhibitors and narcotic analgesics * Subject taking any immunosuppressant within 28 days prior to Visit 1 * Subject has a history of suicide attempt, has received professional counseling for suicidal ideation, or is currently experiencing active suicidal ideation * Subject has a seizure disorder characterized primarily by isolated auras (ie, simple partial seizures without observable motor signs) * Subject suffering from seizures other than partial (IA, IB, IC, with clear focal origin) seizures * Subject has a history of status epilepticus within last 3-month period prior to Visit 1 * Subject has seizures that are uncountable due to clustering (ie, an episode lasting less than 30 minutes in which several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) during the 12-week period prior to Visit 1 and/or during the Screening Period * Body weight is lower than 40 kg (\< 40 kg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With a Treatment Failure | Week 0 (First Dose) to Week 50 | Treatment failure is defined as (1) Dropout due to related intolerable adverse event, lack of efficacy or need for addition of another Antiepileptic Drug (AED), or (2) need of a 1-step down-Titration, within 50 weeks from the first dose of study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period | From Week 2 to Week 50 (During Treatment Period ) | — |
| Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time | From Week 2 to Week 50 (During Treatment Period ) | 24-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom for 24 consecutive weeks during the Treatment Period at any time |
| Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period | From Week 2 to Week 50 (During Treatment Period ) | 48-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom during the Treatment Period |
Countries
South Korea
Participant flow
Recruitment details
This study started to enroll subjects in June 2011. A total of 27 investigators enrolled 353 subjects at 23 sites in Korea.
Pre-assignment details
Participant Flow refers to the Randomized Set, consisting of all subjects who were randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Levetiracetam twice a day treatment Group
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks | 175 |
| Oxcarbazepine Oxcarbazepine twice a day treatment Group
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week) | 178 |
| Total Title | 353 |
| Total | 706 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event, serious fatal | 1 | 1 |
| Overall Study | AE, non-serious non-fatal | 8 | 17 |
| Overall Study | Lack of Efficacy | 7 | 2 |
| Overall Study | Lost to Follow-up | 8 | 3 |
| Overall Study | Other Reason | 5 | 2 |
| Overall Study | Protocol Violation | 8 | 4 |
| Overall Study | SAE, non-fatal | 2 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 25 |
Baseline characteristics
| Characteristic | Levetiracetam | Oxcarbazepine | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 13 Participants | 27 Participants |
| Age, Categorical >=65 years | 16 Participants | 22 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 145 Participants | 143 Participants | 288 Participants |
| Age, Continuous | 39.5 years STANDARD_DEVIATION 16.7 | 42.7 years STANDARD_DEVIATION 17.3 | 41.1 years STANDARD_DEVIATION 17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 174 Participants | 178 Participants | 352 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 84 Participants | 79 Participants | 163 Participants |
| Sex: Female, Male Male | 91 Participants | 99 Participants | 190 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 173 | 93 / 174 |
| serious Total, serious adverse events | 15 / 173 | 15 / 174 |
Outcome results
Primary
Percentage of Subjects With a Treatment Failure
Treatment failure is defined as (1) Dropout due to related intolerable adverse event, lack of efficacy or need for addition of another Antiepileptic Drug (AED), or (2) need of a 1-step down-Titration, within 50 weeks from the first dose of study medication.
Time frame: Week 0 (First Dose) to Week 50
Population: Per Protocol Set (PPS) consisted of all subjects who received at least 1 (partial) dose of study mediaction, returned at least 1 post-Baseline seizure diary and had no important protocol deviations. Subjects who discontinued the study before Week 50 for any reason other than treatment failure were excluded from the PPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Per Protocol Set (LEV Treated Subjects) | Percentage of Subjects With a Treatment Failure | 12.7 percentage of subjects |
| Per Protocol Set (OXC Treated Subjects) | Percentage of Subjects With a Treatment Failure | 23.4 percentage of subjects |
95% CI: [-20.2, -1.2]Wald methodology
Secondary
Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period
48-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom during the Treatment Period
Time frame: From Week 2 to Week 50 (During Treatment Period )
Population: The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.~A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Per Protocol Set (LEV Treated Subjects) | Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period | 34.7 percentage of subjects |
| Per Protocol Set (OXC Treated Subjects) | Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period | 40.9 percentage of subjects |
Secondary
Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time
24-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom for 24 consecutive weeks during the Treatment Period at any time
Time frame: From Week 2 to Week 50 (During Treatment Period )
Population: The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.~A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Per Protocol Set (LEV Treated Subjects) | Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time | 53.8 percentage of subjects |
| Per Protocol Set (OXC Treated Subjects) | Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time | 58.5 percentage of subjects |
Secondary
Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period
Time frame: From Week 2 to Week 50 (During Treatment Period )
Population: The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.~A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Per Protocol Set (LEV Treated Subjects) | Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period | 7.556 months |
| Per Protocol Set (OXC Treated Subjects) | Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period | NA months |