Epilepsy
Conditions
Brief summary
The object of this study is to assess the efficacy and safety of zonisamide as adjunctive therapy in patients with uncontrolled partial epilepsy.
Detailed description
The object of this study is to assess the efficacy and safety of zonisamide as adjunctive therapy in patients with uncontrolled partial epilepsy. Subject takes zonisamide for 16 weeks (4 weeks-titration period, 8 weeks maintenance period). Dose range of zonisamide is 100 \ 400 mg/day and target dose is 300 mg/day. After 16 weeks, zonisamide efficacy is measured by seizure reduction rate (Each type of seizure: simple partial seizures \[SPS\], complex partial seizures \[CPS\], simple partial seizures evolving into generalized tonic-clonic convulsions \[SGTC\] and total seizure frequency), seizure free rate, responder rate, quality of life in epilepsy (QOLIE-31) and investigator's global evaluation scale. Safety of zonisamide in this study will be estimated by adverse event profile, retention rate and dose of exposure. The duration of this clinical study is 2 years including period of subject enrollment.
Interventions
DRUGzonisamide
zonisamide 100 mg tablet
Sponsors
Eisai Korea Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Epilepsy patient over 15 years old who agrees with Informed Consent Form 2. Patient who has classifiable uncontrolled partial epilepsy according to International Classification of Epileptic Seizures. 3. Patient who has 3 \ dozens of partial seizure (average more than once seizure per 4 weeks) last 12 weeks despite taking 1 \ 3 antiepileptic drug(s). 4. Patient who takes 1 \ 3 marketed antiepileptic drug(s) excluding zonisamide at point of enrollment time. 5. Before study visit, patient who takes stable dose of antiepileptic drug more than 4 weeks.
Exclusion criteria
1. Patient who has progressive central nervous system (CNS) disorder and/or degenerative disease of the brain. 2. Patient who experiences pseudoseizures and/or who has uncountable clusters. 3. Patient who has serious systemic or drug metabolism affecting disorder . 4. Upward of doubled normal glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), bilirubin, blood urea nitrogen (BUN), creatinine levels. 5. Patient who has absolute neutrophil counts \<1800/mm3 or platelets \<100,000/mm3. 6. Patient who has medical history of renal stones. 7. Patient who is allergic to sulfonamide. 8. Medical history of medicinal poisoning and/or alcoholism and/or serious psychological disorder. 9. Pregnant women, lactating women, women of childbearing age who do not use a preventive method of conception. 10. A terminal patient and/or a scheduled surgical patient. 11. Patient who has medication history of zonisamide. 12. Patient who participated other clinical trial within the last 12 weeks at point of enrollment time of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Reduction Rate | Baseline and 16 weeks | The percentage of the seizure reduction after Zonisamide treatment comparing baseline seizure frequency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Free Rate | 16 weeks | The percentage of the participants who experienced no seizure during the trial. |
| Responder Rate | Baseline and 16 weeks | The percentage of participants whose median percentage change in seizure frequency after Zonisamide treatment is reduced over 50%. |
| QoL-QOLIE31 (Quality of Life in Epilepsy) | Baseline and 16 weeks | Quality of life assessment tool. Overall scores is calculated by summing subsections, and it ranges from 0 to 100. Higher score presents higher quality of life. |
Countries
South Korea
Participant flow
Recruitment details
This study was recruited at 10 centers in Korea during the period of February 2008 to August 2010.
Participants by arm
| Arm | Count |
|---|---|
| Zonisamide Initial dose was 100mg/day, increased by 100mg in week 2 and 4. The target dose was 300mg/day, and the maximum dose was 400mg/day. | 121 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 22 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Medication Noncompliance | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Uncooperative patient | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Zonisamide |
|---|---|
| Age, Continuous | 37.70 years STANDARD_DEVIATION 11.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 121 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 78 / 121 |
| serious Total, serious adverse events | 2 / 121 |
Outcome results
Primary
Seizure Reduction Rate
The percentage of the seizure reduction after Zonisamide treatment comparing baseline seizure frequency.
Time frame: Baseline and 16 weeks
Population: Efficacy analyses were based on the FAS (Full analysis set) population, which was comprised of all patients who administrated Zonisamide at least once and reached the maintenance period to evaluate the primary endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zonisamide | Seizure Reduction Rate | -16.35 Percentage of Seizure Reduction Rate | Standard Deviation 436 |
Secondary
QoL-QOLIE31 (Quality of Life in Epilepsy)
Quality of life assessment tool. Overall scores is calculated by summing subsections, and it ranges from 0 to 100. Higher score presents higher quality of life.
Time frame: Baseline and 16 weeks
Population: Efficacy analyses were based on the FAS (Full analysis set) population, which was comprised of all patients who administrated Zonisamide at least once and reached the maintenance period to evaluate the primary endpoint. Regarding QOLIE-31, among FAS population, the patients who have both of baseline and 16 week evaluation are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | QoL-QOLIE31 (Quality of Life in Epilepsy) | Baseline- Pre-QOLIE 31 total score (N=90) | 56.67 Units on a Scale | Standard Deviation 15.97 |
| Zonisamide | QoL-QOLIE31 (Quality of Life in Epilepsy) | 16 weeks - Post- QOLIE 31 total score (N=90) | 57.70 Units on a Scale | Standard Deviation 15.74 |
Secondary
Responder Rate
The percentage of participants whose median percentage change in seizure frequency after Zonisamide treatment is reduced over 50%.
Time frame: Baseline and 16 weeks
Population: Efficacy analyses were based on the FAS (Full analysis set) population, which was comprised of all patients who administrated Zonisamide at least once and reached the maintenance period to evaluate the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zonisamide | Responder Rate | 61.76 Percentage of Participants |
Secondary
Seizure Free Rate
The percentage of the participants who experienced no seizure during the trial.
Time frame: 16 weeks
Population: Efficacy analyses were based on the FAS (Full analysis set) population, which was comprised of all patients who administrated Zonisamide at least once and reached the maintenance period to evaluate the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zonisamide | Seizure Free Rate | 24.51 Percentage of Participants |