A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures

A Randomised, Double Blind, Placebo-controlled Study to Evaluate the Safety and Tolerability and to Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures

A two arm, randomized, double-blind study comparing zonisamide with placebo. The zonisamide arm will consist of 100 subjects and the placebo arm of 50 subjects. Study medication will be administered as an add-on treatment to the subject's current 1 or 2 anti-epileptic (AEDs).

Study Overview

• Status: Terminated
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Zonisamide at targeted daily doses of 100-500 mg/day; Drug: Placebo administered to match targeted daily doses of 100-500 mg/day

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany
    • Klinik und Polyklinik fur Epileptologie
  • Gottingen, Germany
    • Georg-August-Universiat Gottingen
  • Hamburg, Germany
    • Clinical Research Hamburg
  • Hamburg, Germany
    • Asklepiosklinik Barmbek
  • Hamburg, Germany
    • ZNS Hamburg
  • Marburg, Germany
    • Universitaet Giessen / Marburg
  • Siegen, Germany
    • Neurologische
• Hungary
  • Budapest, Hungary, 1145
    • National Institute of Neurosurgery
  • Budapest, Hungary, 1083
    • Semmelweis University - Neurology Dept.
  • Budapest, Hungary, 11036
    • Synexus Magyarorszag Kft.
  • Keskemet, Hungary, 6000
    • County Hospital Kecskemet
  • Miskolc, Hungary, 3501
    • B-A-Z County Hospital - Szuleszet-Nogyogyaszat
  • Sopron, Hungary, 9400
    • Sopron Medical SMO
  • Szeksz?rd, Hungary, 7100
    • County Hospital of Tolna
  • Zalaegerszeg, Hungary, 8900
    • County Hospital of Zala
• Italy
  • Cagliari, Italy, 00134
    • S.C. Neurologia - AO "G.Brotzu"
  • Firenze, Italy, 50134
    • Dip. Di neuroscienze - Centro Epilessie - Osp. Careggi
  • Napoli, Italy, 80131
    • Dipartimento di Neuroscienze - Universita Federico II
  • Pavia, Italy, 27100
    • Centro Epilessia - Istituto Neurologico "Fondazione C. Mondino"
  • Pavia, Italy, 27100
    • Centro per la Diagnosi e Cura dell'epilessia - Policlinico Universitario di Messina
  • Roma, Italy, 00185
    • Dip.to Scienze Neurologiche - III Clinica Neurologica
  • Torino, Italy, 10126
    • Universita di Torino - Dipt. Neuroscienze
• Netherlands
  • VA Den Haag, Netherlands, 2512
    • Medisch Centrum Haaglanden - Lokatie Westeinde
• Poland
  • Kalisz, Poland, 62-800
    • Specjalistyczny Zaklad Opieki Zdrowotnej 'KONSYLIUM'
  • Katowice, Poland, 40- 097
    • Specjalistyczna Praktyka Lekarska
  • Leszno, Poland, 64-100
    • NZOZ Centermed Gabinety ?lnolekarskie
  • Lublin, Poland, 20-090
    • Przych. Specj. I chorob Zaw. Wsi Instytut Medyc. Wsi im. W. Chodzki
  • Olsztyn, Poland, 10-561
    • Oddzia Neurologiczny, Wojewdzki Szpital Specjalistyczny
  • Pozna, Poland, 61-489
    • NZOZ Centrum Medyczne HCP
  • Warszawa, Poland, 03-464
    • Wielospecjalistyczna Lecznica 'Zycie'
• Switzerland
  • Bern, Switzerland, 3010
    • Clinical Investigation Unit; Inselspital
  • Biel, Switzerland, 2501
    • Spitalzentrum Biel
  • Zurich, Switzerland, 8008
    • Epilepsie-Zentrum
• United Kingdom
  • London, United Kingdom, E11 1NR
    • Whipps Cross University Hospital
  • Stoke-on-Trent, United Kingdom, ST4 7LN
    • University Hospital of North Staffordshire
  • Truro, United Kingdom, TR1 3LJ
    • The Royal Cornwall Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Capable of maintaining a seizure daily diary or who have access to a caregiver who is prepared to complete this on the patient's behalf.
2. Able to complete the questionnaires used in this study.
3. Localization related epilepsy, with simple and/or complex partial seizures with or without secondary generalized seizures as defined by the International League Against Epilepsy (ILAE) criteria.
4. Have at least one well documented seizure in the 4 weeks preceding the Randomisation Visit (Visit 2) and are deemed to require additional AED medication.
5. Receiving at least one, but not more than two other marketed AEDs as concomitant medication, and the dosage should be stable for at least four weeks before the Screening Visit.

Key Exclusion Criteria:

1. Seizures attributed to metabolic causes (e.g., electrolyte disturbances, hyperglycaemia).
2. Seizures which could be attributed to use of a drug.
3. Presence of primary generalised epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
4. A history of eating disorders or a body weight below 40 kg.
5. A history of blood dyscrasias.
6. A history of renal stones or having risk factors for nephrolithiasis such as a family history of nephrolithiasis or hypercalciuria.
7. An increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism, personal or family history of muscle disorders.
8. Taking concomitant medication associated with nephrolithiasis and medications increasing the risk of rhabdomyolysis.
9. Taking rifampicin or drugs with anticholinergic effects.
10. Taking carbonic anhydrase inhibitors or topiramate.
11. A history of pancreatitis.
12. A history of Stevens Johnson Syndrome.
13. Elevated levels of serum creatinine >165 Umol, or known severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zonisamide at targeted daily doses of 100-500 mg/day	Drug: Zonisamide at targeted daily doses of 100-500 mg/day; Each group received 2 doses a day (in the morning and evening) during the Titration Period, once a day (in the evening) or BID during the Maintenance Phase, comprising 25 mg, 50 mg, or 100 mg of ZNS capsules
Placebo Comparator: Placebo administered to match daily doses of 100-500 mg/day	Drug: Placebo administered to match targeted daily doses of 100-500 mg/day; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CVST of the FePsy Test (Mean Reaction Time) by Visit During Titration and Maintenance Period	The Computer Visual Search Task (CVST) of the Ferrum Psyche (FePsy)measured cognition. A decrease from Baseline (negative change value) signifies an improvement in the mean reaction time of CVST.	Baseline, Week 4, Week 8, Week 12, Week 16
Change From Baseline in Bond and Lader Visual Analogue Scale (VAS) Mood Sub-Scores for Sedation by Visit During Titration and Maintenance Period	The Bond-Lader mood rating scale measured sedation, with scores ranging from 0 to 100. A high score reflects a high level of sedation.	Baseline, Week 4, Week 8, Week 12, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Seizure Frequency From Baseline to the Last 28 Days of the Maintenance Period	Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure.	Baseline and Month 4
Percentage of Responders During Last 28 Days of Maintenance Period	Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure. A responder is a subject who had at least a 50 percent or greater reduction in the seizure frequency of all seizures during the last 28 days of the Maintenance Period compared to the Baseline Period seizure frequency. Due to the exploratory nature of the objective for efficacy and the truncated study size, analysis of efficacy was based on observed cases, without imputation for missing data. As a result, there are some variations in sample sizes for efficacy at different visits, depending on if particular efficacy variables were missing for particular visits.	Baseline and Month 4

Collaborators and Investigators

• Sponsor: Eisai Limited
• Investigators: Study Director: Joanna Segieth, Eisai Limited

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 2, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (Estimate): March 7, 2012

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: November 1, 2015

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-E044-402; 2006-002516-10 (EudraCT Number)