Evaluation of the Efficacy and Safety of Adjunctive Zonisamide vs Replacement With Zonisamide of the Last Added Antiepileptic Drug

Study Overview
=================
Brief Summary
-----------------
An open-label, randomized, multi-centre, superiority study to assess that, in patients who respond to zonisamide added as third drug after failure of a two-drug combination therapy, the triple therapy is superior to the conversion to a double therapy including zonisamide.

Official Title
-----------------
An Open-label, Randomized, Multi-centre, Superiority Study to Compare, in Patients With Partial Onset Seizures, the Efficacy and Safety of Adjunctive Zonisamide vs Replacement With Zonisamide of the Last Added Antiepileptic Drug

Conditions
-----------------
Partial Seizures

Intervention / Treatment
-----------------
* Drug: Adjunctive Zonisamide
* Drug: Replacement with Zonisamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Patients with localization-related epilepsy, who have added a second drug to the monotherapy, haven't obtained an adequate reduction of seizure frequency with this combination and have responded to zonisamide added as third drug for at least three months. Inclusion criteria: Age ≥ 18 years; Patients with non progressive localization-related epilepsy; Patients who are able and willing to give written Informed Consent; Current treatment with three antiepileptic drugs. The last antiepileptic drug introduced must be zonisamide; 50% or greater seizure reduction* as assessed after an at least three-month maintenance period with zonisamide. = seizure frequency before starting zonisamide must be documented checking case histories. Exclusion criteria: Patients contraindicated for zonisamide use (see SmPC); Patients with renal or hepatic impairment; Pregnant or lactating women; Women of childbearing age who are not willing to use any contraceptive method with established efficacy. Patients suffering from clinically significant psychiatric illness, psychological or behavioral problems which could interfere with study participation; Patients with a history (within the last 12 months) of alcohol or drug abuse or dependency; Patients who have been on an investigational drug or device within 30 days prior to the initiation of the present study; Patients with a documented computed axial tomography (CAT) scan or magnetic resonance imaging (MRI) scan confirming the presence of a progressive neurological lesion within 12 months of the screening visit.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjunctive Zonisamide<br>Patients will be gradually down-titrated from the first add-on following a drug-specific scheme decided by the investigator. Discontinued from the first add-on, patients will remain on duotherapy until the end of the study, or until the clinical situation mandates withdrawal from the study, e.g. in case of seizure worsening or adverse events. | Drug: Adjunctive Zonisamide<br>* Patients will be gradually down-titrated from the first add-on following a drug-specific scheme decided by the investigator. Discontinued from the first add-on, patients will remain on duotherapy until the end of the study, or until the clinical situation mandates withdrawal from the study, e.g. in case of seizure worsening or adverse events.<br>|
| Active Comparator: Replacement with Zonisamide<br>Patients will continue to receive zonisamide as third drug | Drug: Replacement with Zonisamide<br>* Patients will continue to receive zonisamide as third drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability in patients who respond to zonisamide added as third drug after failure of a two-drug combination therapy |  | 13 months |