Epilepsy
Conditions
Keywords
Epilepsy, Topiramate, Neuro-surgical patients, Nervous disorder, Seizures
Brief summary
The purpose of this study is to examine seizure control and tolerability of Topiramate after either transitioning from previous antiepileptic drug (AED) or adding on to previous AED.
Detailed description
This is a multicenter, randomized (treatment is assigned by chance), open-label (everyone who is involved in the trial knows the study drug), parallel group trial. The study has three phases: a retrospective baseline assessment of patients (4 weeks), titration period (8 weeks) and maintenance period (8 weeks). After qualifying for trial entry in the retrospective baseline phase, eligible patients will be randomized in 1:1 ratio to receive either topiramate add-on therapy or topiramate monotherapy. During the titration period (period in which the dose of the study drug is increased or decreased at the discretion of investigator), topiramate, given as morning doses, will be started with daily doses of 25 mg/day for one week. After that, topiramate will be given as morning and evening doses, and the doses will be gradually increased every week to reach the initial target dose of 200 mg/day at the end of titration period. During the maintenance period, the dose of topiramate could be increased or decreased according to the investigator's judgment. Patients should keep seizure diaries during the 16 weeks of topiramate treated period and are followed with once monthly visits to the clinic, at which safety will be evaluated.
Interventions
DRUGTopiramate add-on therapy
Type=range, unit=mg/day, number=25-200, form=tablet, route=oral use.
DRUGTopiramate monotherapy
Type= range, unit= mg/day, number= 25-200, form= tablet, route= oral use.
Sponsors
Johnson & Johnson Taiwan Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must be diagnosed with seizure disorder * Have been receiving concomitant therapy with one antiepileptic drug (AED), at stable dose prior to trial entry * Must be dissatisfied with the current treatment
Exclusion criteria
* Have treatable cause of seizures (eg, metabolic disturbance, toxic exposure, an active infection, or neoplasm) * Have grade IV astrocytomas, eg, Glioblastoma multiforme (GBM) or metastases with progression * Have seizures occurring only in clustered patterns defined as numerous seizures occurring in less than 30 min * Have had history (within past six months) of a psychiatric or mood disorder requiring electroconvulsive therapy, major tranquilizers, or monoamine oxidase inhibitors * Have had schizophrenic or history of exhibiting psychotic symptomatology * Inability to take medication or maintain a seizure calendar, independently or with assistance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4). | Month 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4 | Baseline (4 weeks retrospective assessment prior to start of titration period) to Month 4 | Seizure frequency (seizure count/month) was calculated based on the number of seizure within a month. The mean seizure frequency analyzed by the ANCOVA model at each period. |
| Dosage Administration of Topamax During Month 4 | Month 4 | — |
Participant flow
Recruitment details
55 participants were randomly assigned to receive either topiramate monotherapy or add-on therapy at 6 sites in Taiwan.
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Monotherapy Participants received a starting dose of 25 mg/day during week 1 and the dosage increased to 50 mg/day in 2 doses during week 2. Consequently, the dosage increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage increased to 150 mg/day in 2 doses at week 5\
6 and 200 mg/day in 2 doses at week 7\
8. | 35 |
| Topiramate add-on Therapy Participants received topiramate in addition to previous ant-epileptic drug. Participants received a starting dose of 25 mg/day in the morning during week 1 and the dosage was increased to 50 mg/day in 2 doses (morning and evening) during week 2. Consequently, the dosage was increased to 75 mg/day and 100 mg/day in 2 doses during week 3 and week 4, respectively. The dosage was increased to 150 mg/day in 2 doses at week 5\
6 and 200 mg/day in 2 doses at week 7\
8. | 20 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Seizure frequency doubled | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Topiramate Monotherapy | Topiramate add-on Therapy | Total |
|---|---|---|---|
| Age Continuous | 44.1 years STANDARD_DEVIATION 11.91 | 42.4 years STANDARD_DEVIATION 12.21 | 43.17 years STANDARD_DEVIATION 11.41 |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 22 Participants | 13 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 35 | 20 / 20 |
| serious Total, serious adverse events | 1 / 35 | 1 / 20 |
Outcome results
Primary
Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4).
Time frame: Month 4
Population: Intent-To-Treat population: All randomized participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate Monotherapy | Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4). | 88.57 Percentage of participants |
| Topiramate add-on Therapy | Seizure Free Rate: Percentage of Participants Who Did Not Have Any Seizure Episode Within the Last Month of the Maintenance Period (ie, Month 4). | 65.00 Percentage of participants |
p-value: 0.075995% CI: [-4.21, 49]ANOVA
Secondary
Dosage Administration of Topamax During Month 4
Time frame: Month 4
Population: Participants who have received study medication during month 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate Monotherapy | Dosage Administration of Topamax During Month 4 | 182.46 mg | Standard Deviation 35.63 |
| Topiramate add-on Therapy | Dosage Administration of Topamax During Month 4 | 178.57 mg | Standard Deviation 41.98 |
Secondary
Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4
Seizure frequency (seizure count/month) was calculated based on the number of seizure within a month. The mean seizure frequency analyzed by the ANCOVA model at each period.
Time frame: Baseline (4 weeks retrospective assessment prior to start of titration period) to Month 4
Population: Intent-To-Treat population: All randomized participants who received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate Monotherapy | Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4 | -55.3 Percent change | Standard Deviation 160 |
| Topiramate add-on Therapy | Seizure Frequency: Percent Change of Seizure Frequency by the ANCOVA Model During the Month 4 | -75.8 Percent change | Standard Deviation 54.1 |
p-value: 0.710295% CI: [-81, 117.7]ANCOVA