Epilepsy
Conditions
Keywords
Epilepsy, Seizures, Topiramate, Anti-epileptic drug, Nervous disorder
Brief summary
The purpose of this dose optimization study is to assess tolerability and efficacy of topiramate monotherapy in recently diagnosed patients with epilepsy who are treatment naive or have failed one anti-epileptic drug (AED) treatment in monotherapy.
Detailed description
This is an open label (all people know the identity of the intervention), dose optimization trial to assess the tolerability and efficacy of topiramate as monotherapy in recently (within 5 years) diagnosed patients with epilepsy. Treatment naive patients (patients who have never received the treatment before) and patients who failed on their first AED in monotherapy are allowed. Failure is defined as a lack of efficacy and/or tolerability of that AED and the reason for failure is recorded by the physician. A lack of efficacy is characterized when the patient has been treated with AED at target dose but the patient still has seizure. Topiramate will first be titrated up to an initial target dose that will be reached after 4-6 weeks. Further dose titration is guided by the clinical response of the individual patient, but the dose may not exceed a maximum of 400mg/day \[9mg/kg/day for children\]. If the patient uses an AED at entry, the AED will be fully tapered off over a period of 3 weeks, starting at the beginning of week 2, in order to have all patients on topiramate monotherapy at visit 3. Tapering the AED off may, however, extend this 3-week period if clinically indicated. Visits will be performed at baseline and after 2, 4, 8, 12, 16 weeks. The total duration for each patient in the study will be 4 months.
Interventions
DRUGTopiramate
The patients will receive topiramate tablet twice daily orally up to 16 weeks.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Has been diagnosed with epilepsy within the past 5 years with Primary Generalized Tonic-Clonic (PGTC) seizures as well as partial onset seizures with or without secondary generalization * Therapy naive, or being treated with their first anti-epileptic drug (AED) in monotherapy that fails in efficacy, tolerability, or both, and not in need of a combination AED therapy * Informed Assent in children at least 7 years and older
Exclusion criteria
* Have pseudoseizures or the treatable cause of the seizures (eg, metabolic disorder, toxic exposure, active infection or neoplasia) * Has any clinically relevant progressive or serious illness (eg, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbance) * Pregnant or breast-feeding * Has a history or suspicion of alcohol or drug abuse * Must have on current treatment with furosemide, hydrochlorothiazide, monoamine oxidase inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment | Month 1, Month 3 and Month 4 |
| Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment | Month 1, Month 3 and Month 4 |
| Percentage of Seizure Free Participants During the Last 4 Months of Treatment | Month 1, Month 3 and Month 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Month 1, Month 3 and Month 4 | — |
| Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | Month 4 | — |
| Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | Month 4 | — |
| General Clinical Assessment Before and After Treatment | Baseline (Day 0) and Month 4 | The general clinical assessment is measured by clinical global impression scale. The scale is used to grade the participants as very good, good, fairly good, medium and Poor before (Visit 1) and after treatment (Visit 6). |
Countries
Vietnam
Participant flow
Recruitment details
139 epileptic participants from three participating centers (Neurological department of the Central (Vietnam-Sweden) Pediatrics Hospital, Neurological department of Children's Hospital N0 II at Ho Chi Minh City and the Children's Outpatient Clinic of the Mental Hospital at Ho Chi Minh City) were enrolled in this study to receive topiramate.
Pre-assignment details
Out of 139 participants, 132 participants were included in the safety analysis, 117 participants completed the trial, entering efficacy analysis and 22 participants were withdrawn from the study.
Participants by arm
| Arm | Count |
|---|---|
| Topiramate The participants will receive an initial dose of 0.5mg/kg per oral in the evening, followed by increasing dosage of 0.5 mg/kg/day every week during 6 weeks until the target dose of 3 mg/kg/day being achieved. Subsequent dose is titrated by increasing 0.5 mg/kg/day every week to reach optimal dose according to efficacy and tolerability, but not exceeding total dose of 9 mg/kg/day. | 139 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Non-compliance | 11 |
| Overall Study | Protocol Violation | 3 |
Baseline characteristics
| Characteristic | Topiramate |
|---|---|
| Age, Continuous | 10.1 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 57 / 132 |
| serious Total, serious adverse events | 0 / 132 |
Outcome results
Primary
Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment
Time frame: Month 1, Month 3 and Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment | Month 1 | 7.0 percentage of participants |
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment | Month 3 | 2.4 percentage of participants |
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment | Month 4 | 3.0 percentage of participants |
Primary
Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment
Time frame: Month 1, Month 3 and Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment | Month 1 | 20.3 percentage of participants |
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment | Month 3 | 16.9 percentage of participants |
| Topiramate | Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment | Month 4 | 16.0 percentage of participants |
Primary
Percentage of Seizure Free Participants During the Last 4 Months of Treatment
Time frame: Month 1, Month 3 and Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Seizure Free Participants During the Last 4 Months of Treatment | Month 1 | 58.6 percentage of participants |
| Topiramate | Percentage of Seizure Free Participants During the Last 4 Months of Treatment | Month 3 | 67.0 percentage of participants |
| Topiramate | Percentage of Seizure Free Participants During the Last 4 Months of Treatment | Month 4 | 70.0 percentage of participants |
Secondary
General Clinical Assessment Before and After Treatment
The general clinical assessment is measured by clinical global impression scale. The scale is used to grade the participants as very good, good, fairly good, medium and Poor before (Visit 1) and after treatment (Visit 6).
Time frame: Baseline (Day 0) and Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 1: Very good | 0.0 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 6: Very good | 17.9 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 1: Good | 1.4 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 6: Good | 52.8 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 1: Fairly good | 37.7 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 6: Fairly good | 25.2 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 1: Medium | 44.9 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 6: Medium | 1.6 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 1: Poor | 15.9 percentage of participants |
| Topiramate | General Clinical Assessment Before and After Treatment | Visit 6: Poor | 2.4 percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks
Time frame: Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | < 4 seizures/month with ≥50% | 3.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | < 4 seizures/month with ≥75% | 5.7 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | < 4 seizures/month 100% | 74.3 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | 4-10 seizures/month with ≥50% | 5.7 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | 4-10 seizures/month with ≥75% | 11.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | 4-10 seizures/month with 100% | 71.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | >10 seizures/month with ≥50% | 0.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | >10 seizures/month with ≥75% | 28.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks | >10 seizures/month with 100% | 66.0 percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks
Time frame: Month 1, Month 3 and Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Partial seizures with 100% | 65.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Partial seizures with ≥50% | 3.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Secondarily generalized seizure with ≥50% | 3.3 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Generalized tonic clonic seizure with ≥50% | 2.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Partial seizures with ≥75% | 17.5 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Secondarily generalized seizure with ≥75% | 26.7 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Generalized tonic clonic seizure with ≥75% | 10.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Secondarily generalized seizure with 100% | 60.0 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks | Generalized tonic clonic seizure with 100% | 80.0 percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment
Time frame: Month 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIth previous treatment ≥50% | 2.3 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIth previous treatment ≥75% | 11.4 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIth previous treatment 100% | 70.5 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIthout previous treatment ≥50% | 2.7 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIthout previous treatment ≥75% | 19.2 percentage of participants |
| Topiramate | Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment | WIthout previous treatment 100% | 69.9 percentage of participants |