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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier:
NCT01546688
First received: March 2, 2012
Last updated: June 30, 2014
Last verified: February 2013
  Purpose

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).


Condition Intervention Phase
Epilepsy
Drug: Zonisamide at targeted daily doses of 100-500 mg/day
Drug: Placebo administered to match targeted daily doses of 100-500 mg/day
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Change From Baseline in CVST of the FePsy Test (Mean Reaction Time) by Visit During Titration and Maintenance Period [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Bond and Lader Visual Analogue Scale (VAS) Mood Sub-Scores for Sedation by Visit During Titration and Maintenance Period [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ] [ Designated as safety issue: No ]
    The Bond-Lader mood rating scale measured sedation, with scores ranging from 0 to 100. A high score reflects a high level of sedation.


Secondary Outcome Measures:
  • Percent Change in Seizure Frequency From Baseline to the Last 28 Days of the Maintenance Period [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]
    Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure.

  • Percentage of Responders During Last 28 Days of Maintenance Period [ Time Frame: Baseline and Month 4 ] [ Designated as safety issue: No ]
    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.


Enrollment: 41
Study Start Date: November 2008
Study Completion Date: August 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546688

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

No publications provided

Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT01546688     History of Changes
Other Study ID Numbers: E2090-E044-402, 2006-002516-10
Study First Received: March 2, 2012
Results First Received: November 12, 2012
Last Updated: June 30, 2014
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Zonisamide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014