A Study to Assess Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Open Flexible Dose Optimisation Trial Assessing Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy Who Are Treatment Naive or Have Failed One Anti-Epileptic Drug Treatment in Monotherapy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topiramate<br>For children: Children will start on topiramate with a dosage of 0.5mg/kg in the evening, followed by 0.5mg/kg/day weekly increments until an initial target dose of 3mg/kg/day is reached. The total daily topiramate dose for children may, not exceed 9mg/kg/day. For adult patients: Adult patients start on topiramate with a dosage of 25mg/day in the evening, followed by weekly increments of 25 mg/day until an initial target dose of 100mg/day is reached. The dose of topiramate may be increased to the optimal dose with weekly increments of 0.5mg/kg/day and of 25 mg/day for children and adults, respectively at the discretion of the investigator. | Drug: Topiramate<br>* The patients will receive topiramate tablet twice daily orally up to 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 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). | Baseline (Day 0) 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Seizures, Topiramate, Anti-epileptic drug, Nervous disorder