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Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)
This study is currently recruiting participants.
Verified by Eisai Inc., August 2009
First Received: November 29, 2007   Last Updated: September 1, 2009   History of Changes
Sponsor: Eisai Inc.
Information provided by: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00566254
  Purpose

The purpose of this study is to compare the safety and efficacy of zonisamide with placebo.


Condition Intervention Phase
Epilepsy; Paediatric Partial Onset Seizures
Drug: Zonisamide
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Double-blind, Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • The objective of this trial is to assess the efficacy of zonisamide in paediatric epilepsy subjects with partial onset seizures treated with one or two other anti-epileptic drugs (AEDs). [ Time Frame: 28 - 32 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To further explore the efficacy and safety of zonisamide. To explore the effect of zonisamide on cognition and growth and development. [ Time Frame: 28 - 32 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 266
Study Start Date: November 2007
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Placebo Comparator Drug: Zonisamide
8mg/kg per day for approximately 24 weeks.

Detailed Description:

This will be a double-blind, randomised, study comparing zonisamide with placebo: each arm will consist of 133 subjects. Zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at weekly intervals until a dose of 8 mg/kg is reached at the end of Week 8. In the event of dose limiting adverse events (AEs), during the eight week Titration Period, one down titration to a lower dose is permitted, this can happen at any point in the Titration Period. Subjects who require further down titration steps will be withdrawn from the study. During the Maintenance Period the dose of study medication must remain unchanged.

Changes in concomitant AEDs are not permitted during the Screening, Titration or Maintenance Periods.

This trial consists of the following periods:

  1. Screening Period (duration eight weeks): once the Screening Visit has been performed, a seizure diary will be maintained to document the baseline seizure frequency in the eight weeks between the Screening Visit and the Randomisation Visit.
  2. Titration Period (duration eight weeks): during this period, zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at one week intervals until a dose of 8 mg/kg is reached at Visit 6 (Week 8). In the event of dose limiting AEs during the Titration Period, one down titration step to the previous dose will be permitted.
  3. Maintenance Period (duration 12 weeks): during this period, randomised subjects will be treated with the dose of zonisamide/placebo which they were receiving at Visit 6 (Week 8). No changes to the dose are allowed during this phase.

Following the Maintenance Period subjects will have the opportunity to enter an open label extension study. This open label extension study will be the subject of a separate protocol and will not be discussed further at this time.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is male or female aged 6-17 years inclusive.
  2. Parent/guardian is willing to sign an approved informed consent form, and accompany the subject on all study visits.
  3. Subject is willing to give informed (written or verbal) assent and if appropriate written informed consent.
  4. Subject has a clinical diagnosis of epilepsy with partial-onset seizures with or without secondary generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981).
  5. Diagnosis has been established by clinical history, electroencephalogram (EEG) and computed tomography/ magnetic resonance imaging (CT/MRI) of the brain consistent with localization related epilepsy.
  6. Subject has > four (simple or complex) partial seizures (with or without secondary generalization) per month over the eight week Screening Period with at least one seizure in each four week period and with no 21 day period being seizure free.
  7. Subject is taking a stable regimen of one or two other AEDs for at least one month prior to Visit 1 (start of the Screening Period).

    NOTE: If using a vagal nerve stimulator (VNS), it must have been implanted for at least five months and stimulator parameters must remain unchanged for at least one month prior to Visit 1 (start of the Screening Period), and throughout the entire study period. VNS will be considered as one AED for the purposes of this study.

  8. Subject is in general good health as determined by medical history, physical exam and screening laboratory results.
  9. Parent/guardian is willing and able to complete a seizure diary for the duration of the study.

Exclusion Criteria:

  1. Subject of body weight < 20 kg at the Screening Visit.
  2. Subject is unable to swallow capsules.
  3. Subject has progressive neurological disease (determined by diagnosis or a pre-existing brain image such as a CT scan or MRI).
  4. Subject has a history of idiopathic generalized epilepsy as defined by the International League Against Epilepsy (ILAE).
  5. Subjects with Lennox-Gastaut syndrome, absence, myoclonic, clonic and/or tonic (other than secondary generalized) and atonic seizures.
  6. Subject has psychogenic seizures
  7. Subject has a history of status epilepticus within a year of the Screening Visit whilst taking AEDs.
  8. Subject has seizures that only occur in clustered patterns, or has seizures that are too close together to count accurately.
  9. Subject has a history of renal calculi or renal insufficiency (creatinine levels >194 µmol/l (1.5 mg1/dl).
  10. Subject had a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
  11. Subject has a history of psychiatric illness.
  12. Subject has a history of suicide attempt.
  13. Female subject who is pregnant or lactating.
  14. Subject has a history of demonstrated non-compliance with treatment or, the subject, parent or legal guardian can be reasonably expected not to be compliant with study procedures or to complete the study.
  15. Female subject of 10 years of age or greater or of child bearing potential (i.e., started menses) and is not taking or prepared to take a medically acceptable form of contraception (i.e., oral contraceptive pill, surgical sterilization, an implant or an injected form of contraception, or intrauterine device), or who is not prepared to abstain from sexual activity for the duration of the study and one month after last administration of study medication.

    NOTE: Should a female subject become of childbearing potential during the study, they must be reconsented in order to give consent to undergo pregnancy testing and either confirm abstinence or receive medically appropriate form of contraception.

  16. Subject has clinically significant abnormal laboratory values at the Screening Visit.
  17. Subject has received previous treatment with zonisamide.
  18. Subject is treated with a ketogenic diet or is likely to have surgery for epilepsy in the trial period.
  19. Subject requires frequent rescue benzodiazepines (one or more times a month).
  20. Concomitant use of felbamate or use of felbamate within 2 months prior to Visit 1.
  21. Subject has elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN).
  22. Subject has evidence of significant active and unstable haematological disease; i.e., white blood cell (WBC) count < 2500/µL or an absolute neutrophil count < 1000/µL
  23. Subject with clinically significant active hepatic disease, cardiovascular, metabolic, respiratory, renal, endocrinological and gastrointestinal diseases or any other clinically significant organic disease, within 30 days prior to the Screening Visit.
  24. Subjects with known or suspected history of alcoholism or drug abuse within the previous two years, or a positive finding on urinary drug screening of any drugs other than prescribed medications.
  25. Subjects with any other condition that would make them, in the opinion of the Investigator unsuitable for this study.
  26. Subjects who have participated in a clinical trial involving administration of an investigational compound (including zonisamide) within three months of the Screening Visit.
  27. Subjects with a known or suspected hypersensitivity to zonisamide, or sulphonamides.
  28. Subjects taking acetazolamide, any carbonic anhydrase inhibitors e.g. topiramate, and any drugs with anticholinergic activity.
  29. Subjects who do not have a complete seizure diary during the Screening Period.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00566254

Contacts
Contact: Medical Information Department - Eisai Limited +44 (0)20 8600 1400

  Hide Study Locations
Locations
Belgium
U.Z Gasthuisberg Recruiting
Leuven, Belgium, 3000
U.Z Gent Recruiting
Gent, Belgium, 9000
Universitair Ziekenhuis Brussel Recruiting
Brussels, Belgium, 1090
Universitair Kinderziekenhuis Koningin Fabiola Recruiting
Brussels, Belgium, 1020
Estonia
Tartu University Hospital Recruiting
Tartu, Estonia, 51014
Tallinn Children's Hospital Recruiting
Tallinn, Estonia, 13419
France
Hopital Charles Nicolle Recruiting
Rouen, France, 76031
CHRU Roger Salengro Recruiting
Lille, France, 59037
CHU Timone Enfants Recruiting
Marseille cedex 05, France, 13385
Hopital Necker Recruiting
Paris, France, 75015
Hopital Raymond Poincare Recruiting
Garches, France, 92380
Hopital des Enfants, CHU Pellegrin Recruiting
Bordeaux, France, 33076
Hungary
Paediatric Clinic Recruiting
Pecs, Hungary, 7623
Bethesda Children Hospital Budapest Recruiting
Budapest, Hungary, 1143
Semmelweis University Recruiting
Budapest, Hungary, 1097
Budai Gyermekkorhaz Kht. Epilepsy Center Recruiting
Budapest, Hungary, 1025
Borsod-Abauj-Zemplen County Hospital Recruiting
Miskolc, Hungary, 3526
Paediatric Clinic, University Debrecen Recruiting
Debrecen, Hungary, 4012
Italy
Ospedali Civili Recruiting
Brescia, Italy, 25123
Ospedale Carlo Poma Recruiting
Mantova, Italy, 40100
Istituto Neurologico Casimiro Mondino Recruiting
Pavia, Italy, 27100
U.O. Istituto Nazionale Neurologico Besta Recruiting
Milano, Italy, 20133
Ospedale Maggiore Recruiting
Bologna, Italy, 40133
Ospedale Anna Meyer Recruiting
Firenze, Italy, 50132
Latvia
Children's Clinical University Hospital Recruiting
Riga, Latvia, LV-1004
Health Centre of Valmiera Recruiting
Valmiera, Latvia, LV-4201
Poland
Specjalistyczny Gabinet Recruiting
Poznan, Poland, 61-493
Samodzielny Publiczny Szpital Kliniczny Recruiting
Katowice, Poland, 40-752
Instytut "Pomnik - Centrum Zdrowia Dziecka" Recruiting
Warszawa, Poland, 04-730
Centrum Neurologii Dzieciecej Recruiting
Olsztyn., Poland, 10-959
Szpital Kliniczny im. H. Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu Recruiting
Poznan, Poland, 60-355
Akademickie Centrum Kliniczne-Szpital AM w Gdansku Recruiting
Gdansk, Poland, 80-952
Spain
Hosp. Clinico San Carlos - Udad.de Neuropediatria Recruiting
Madrid, Spain, 28040
Hosp. Univ. Marques de Valdecilla Recruiting
Santander, Spain, 39008
Hosp. Universitario Virgen del Rocio Recruiting
Sevilla, Spain, 41006
Hosp. San Juan de Deu Recruiting
Barcelona, Spain, 08950
Hosp. Univer. Virgen de la Arrixaca Recruiting
Murcia - El Palmar, Spain, 30120
Hospital Universitario La Paz Recruiting
Madrid, Spain, 2804
Ukraine
Lviv Regional Clinical Hospital Recruiting
Lviv, Ukraine, 79010
Institute of Children and Adolescents Health of AMS of Ukraine Recruiting
Kharkov, Ukraine, 61153
Institute of Neurology, Psychiatry and Narcology Recruiting
Kharkov, Ukraine, 61068
City Children Hospital - Number 5 Recruiting
Dnepropetrovsk, Ukraine, 49027
Odessa SMU, Region Children Clinical Hospital Recruiting
Odessa, Ukraine, 65031
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Rob van Maanen, M.D., MFPM Eisai Limited
  More Information

No publications provided

Responsible Party: Eisai Limited ( Medical Information Department )
Study ID Numbers: E2090-E044-312, 2006-002515-27
Study First Received: November 29, 2007
Last Updated: September 1, 2009
ClinicalTrials.gov Identifier: NCT00566254     History of Changes
Health Authority: European Union: European Medicines Agency

Keywords provided by Eisai Inc.:
Epilepsy
paediatric
partial onset seizures

Additional relevant MeSH terms:
Antioxidants
Molecular Mechanisms of Pharmacological Action
Seizures
Nervous System Diseases
Zonisamide
Physiological Effects of Drugs
Central Nervous System Diseases
Brain Diseases
Protective Agents
Pharmacologic Actions
Signs and Symptoms
Epilepsy
Therapeutic Uses
Neurologic Manifestations
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on November 27, 2009