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

Eisai

Status and phase: Completed; Phase 4

Conditions: Partial Seizures

Treatments: Drug: Replacement with Zonisamide; Drug: Adjunctive Zonisamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01630057

E2090-E039-401

Details and patient eligibility

About

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.

Enrollment: 200 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Adjunctive Zonisamide

Experimental group

Description:

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.

Treatment:

Drug: Adjunctive Zonisamide

Replacement with Zonisamide

Active Comparator group

Description:

Patients will continue to receive zonisamide as third drug

Treatment:

Drug: Replacement with Zonisamide