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

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

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.

Study Overview

• Status: Completed
• Conditions: Partial Seizures
• Intervention / Treatment: Drug: Adjunctive Zonisamide; Drug: Replacement with Zonisamide

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy, 60126
    • AOU Ospedali riuniti Umberto I -G.M Lancisi-G.Salesi
  • Bari, Italy, 70124
    • AO Universitaria Consorziale Policlinico di Bari
  • Bosisio Parini, Italy, 23842
    • Irccs "E. Medea"
  • Cagliari, Italy, 09124
    • Struttura di Neurofisiopatologia, Universit? degli studi di Cagliari
  • Conegliano, Italy, 31015
    • IRCCS "Eugenio Medea" Polo Scientifico di Conegliano
  • Ferrara, Italy, 44100
    • AOU di Ferrara Arcispedale S. Anna
  • Gallarate, Italy, 21013
    • Presidio Ospedale "S.Antonio Abate di Gallarate"
  • L'Aquila, Italy, 67100
    • UOC Neurofisiopatologia PO S. Salvatore
  • Lodi, Italy, 26900
    • AO della Provincia di Lodi
  • Messina, Italy, 98124
    • IRCCS Centro neurolesi "Bonino Pulejo" di Messina
  • Napoli, Italy, 80131
    • AO di Rilievo Nazionale Antonio Cardarelli
  • Napoli, Italy, 80131
    • AO Universitaria Federico II
  • Palermo, Italy, 90127
    • AO Universitaria Policlinico Paolo Giaccone dell'Universit? degli Studi di Palermo
  • Pisa, Italy, 56126
    • AO Universitaria -Pisana
  • Potenza, Italy, 85100
    • AO Regionale "San Carlo" di Potenza
  • Prato, Italy, 59100
    • PO "Misericordia e dolce"-USL 4 di Prato
  • Roma, Italy, 00135
    • Azienda Complesso Ospedaliero San Filippo Neri
  • Roma, Italy, 00161
    • Umberto I Policlinico di Roma
  • Venezia, Italy, 30174
    • Ospedale SS Giovanni e Paolo Azienda ULSS 12 Veneziana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Adjunctive Zonisamide; 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; 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.
ACTIVE_COMPARATOR: Replacement with Zonisamide; Patients will continue to receive zonisamide as third drug	Drug: Replacement with Zonisamide; Patients will continue to receive zonisamide as third drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Principal Investigator: Salvatore Striano, Azienda Ospedaliera Universitaria Federico II

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (ESTIMATE): June 28, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: E2090-E039-401