Epilepsy
Conditions
Keywords
Epilepsy, seizures
Brief summary
The purpose of this study is to evaluate the efficacy and safety of zonisamide for anti-epilepsy drugs (AEDs) treated subjects with refractory simple partial, complex partial or partial with secondary generalized seizures.
Interventions
DRUGZonisamide
Tablet once or twice daily orally for 16 weeks
DRUGLamotrigine
Tablet once daily orally for 16 weeks
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must sign and date the informed consent form * Clinical diagnosis as refractory epilepsy
Exclusion criteria
* Progressive neurologic disease * Serious psychiatric disease * Hemolytic anemia * G6PD (glucose-6-phosphate dehydrogenase) deficiency * Acute intermittent porphyrias * Subjects who have received study drugs (Zonisamide, Lamotrigine) in the past * Drug or alcohol addiction * Renal impairment (serum creatinine ≧ 1.5 mg/dl), or hepatic abnormality (ALT or AST \> 2x ULN) * Stevens-Johnson syndrome * Progressive exfoliative dermatitis * Pregnant, lactating or of childbearing potential female * Regularly taking oral contraceptives * Hypersensitivity to study drugs * Severe cardiac disease (New York Heart Association Functional Class III and IV) * History of malignancy within 5 years * Taking valproic acid within 7 days prior to screening * Subjects with simple partial seizures without motor component
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change of Monthly Seizure Frequency at the End of the 16-week Treatment From Baseline | Baseline and 16 weeks | Percentage Change of Frequency = (T-B)/B\*100% T= Total seizure frequency during maintenance dose period / maintenance dose period (weeks)\* 4 B= The monthly seizure frequence with one month prior to enrollment |
Secondary
| Measure | Time frame |
|---|---|
| Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Baseline and 16 weeks |
| Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Baseline and 16 weeks |
| Response Rate: Defined as the Percentage of Participants With >= 50% Reduction of Monthly Seizure Frequency at the End of 16-week Treatment From Baseline. | Baseline and 16 weeks |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zonegran once or twice daily orally for 16 weeks | 34 |
| Lamotrigine once daily orally for 16 weeks | 30 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Zonegran | Total | Lamotrigine |
|---|---|---|---|
| Age Continuous | 38.3 years STANDARD_DEVIATION 11.5 | 36.8 years STANDARD_DEVIATION 10.8 | 35.0 years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 64 Participants | 30 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 | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 34 participants | 64 participants | 30 participants |
| Sex: Female, Male Female | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Male | 18 Participants | 31 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 34 | 20 / 30 |
| serious Total, serious adverse events | 0 / 34 | 1 / 30 |
Outcome results
Primary
The Percentage Change of Monthly Seizure Frequency at the End of the 16-week Treatment From Baseline
Percentage Change of Frequency = (T-B)/B\*100% T= Total seizure frequency during maintenance dose period / maintenance dose period (weeks)\* 4 B= The monthly seizure frequence with one month prior to enrollment
Time frame: Baseline and 16 weeks
Population: ITT (intent-to-treat)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zonegran | The Percentage Change of Monthly Seizure Frequency at the End of the 16-week Treatment From Baseline | -32.7 percent change |
| Lamotrigine | The Percentage Change of Monthly Seizure Frequency at the End of the 16-week Treatment From Baseline | -35.6 percent change |
p-value: 0.24ANOVA
Secondary
Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period
Time frame: Baseline and 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zonegran | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Somewhat worsened | 3 participants |
| Zonegran | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Greatly improved | 3 participants |
| Zonegran | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Somewhat improved | 14 participants |
| Zonegran | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | No change | 4 participants |
| Zonegran | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Greatly worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Greatly worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | No change | 4 participants |
| Lamotrigine | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Greatly improved | 8 participants |
| Lamotrigine | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Somewhat worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Participants at the End of the 16-week Treatment Period | Somewhat improved | 12 participants |
p-value: 0.079Cochran-Mantel-Haenszel
Secondary
Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period
Time frame: Baseline and 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zonegran | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Somewhat worsened | 0 participants |
| Zonegran | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Greatly improved | 5 participants |
| Zonegran | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Somewhat improved | 9 participants |
| Zonegran | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | No change | 10 participants |
| Zonegran | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Greatly worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Greatly worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | No change | 5 participants |
| Lamotrigine | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Greatly improved | 4 participants |
| Lamotrigine | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Somewhat worsened | 0 participants |
| Lamotrigine | Global Assessment of Efficacy by Physician at the End of 16-week Treatment Period | Somewhat improved | 15 participants |
p-value: 0.46Cochran-Mantel-Haenszel
Secondary
Response Rate: Defined as the Percentage of Participants With >= 50% Reduction of Monthly Seizure Frequency at the End of 16-week Treatment From Baseline.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zonegran | Response Rate: Defined as the Percentage of Participants With >= 50% Reduction of Monthly Seizure Frequency at the End of 16-week Treatment From Baseline. | 45.8 percentage of participants |
| Lamotrigine | Response Rate: Defined as the Percentage of Participants With >= 50% Reduction of Monthly Seizure Frequency at the End of 16-week Treatment From Baseline. | 45.8 percentage of participants |
p-value: 0.86Cochran-Mantel-Haenszel