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Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy

This study has been terminated.
(Sponsor's decision)
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier:
NCT00693017
First received: June 3, 2008
Last updated: June 26, 2014
Last verified: June 2012
  Purpose

This study is intended to provide evidence that zonisamide is safe and effective in the treatment of myoclonic seizures. The total planned trial duration will be 6.5 months. After that, subjects who have completed the study will be eligible to enroll in an open-label extension study until zonisamide is marketed for this indication or further development in this indication stops. This extension study will be described in a separate protocol (E2090-E044-318).


Condition Intervention Phase
Epilepsy
Drug: Zonisamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Number of Participants Considered Responders as Assessed During the Maintenance Period [ Time Frame: Baseline (Week -8 to Week 0) and Maintenance Period (Week 4 to Week 16) ] [ Designated as safety issue: No ]
    The number of participants who were considered responders during the 12 week Maintenance Period (Week 4 to Week 16). A responder was defined as a participant with a decrease >= 50% from baseline in the number of days with myoclonic seizures per 28 days (i.e. 28-day myoclonic seizure frequency in Period from Week 4 to the Week 16 visit compared to Week -8 to randomization at Week 0 [Screening/ Baseline Period]). Occurrence of seizures was documented in a seizure diary. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) and reviewed at each following visit. The diary was completed daily. All seizures except myoclonic seizures were counted individually in the the diary. Due to early termination of the study by the Sponsor, no formal analyses were conducted.


Secondary Outcome Measures:
  • Percentage Change From Baseline in the Monthly Number of Days With Myoclonic Seizures [ Time Frame: Baseline and up to 16 weeks ] [ Designated as safety issue: No ]
    Percentage Change from Baseline in the monthly number of days with myoclonic seizures was assessed both for the Maintenance Period alone (Week 4 to Week 16) and for the entire double-blind treatment period (Week 0 to Week 16). Due to early termination of the study by the Sponsor, no formal analyses were conducted.


Enrollment: 10
Study Start Date: June 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Zonisamide Drug: Zonisamide

50-400 mg capsules once daily in the evening orally.

Maximum study duration 28 weeks comprising:

Baseline Period (Week -8 to Week 0): no treatment

Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4

Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events)

Down Titration Period (4 Weeks)

Other Name: Zonegran
Placebo Comparator: Placebo Drug: Placebo

50-400 mg Zonisamide Placebo capsules once daily in the evening orally.

Maximum study duration 28 weeks comprising:

Baseline Period (Week -8 to Week 0): no treatment

Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4

Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events)

Down Titration Period (4 Weeks)


  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is male or female and aged 12-65 years.
  2. Subject has at least eight days with at least one myoclonic seizure over the two months Baseline Period. Myoclonic seizures must occur in the context of IGE and may be accompanied by other primary generalized seizures, provided these are also consistent with a diagnosis of Idiopathic Generalized Epilepsy (IGE).
  3. Subject (or parent/caregiver, for subjects below the age of consent) is willing to sign an informed consent form. Subjects below the age of consent in their country, must where appropriate be willing to give informed (written or verbal) assent. Subjects from the age specified in local regulations will be required to sign an appropriate informed consent form.
  4. Subject is taking a stable regimen of one or two other AEDs for at least two weeks prior to Visit 1 (start of the Baseline Period).
  5. Subject has a clinical diagnosis of any type of idiopathic generalised epilepsy (IGE) which has myoclonic seizures (and which may be accompanied by other generalised seizure types), according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (1981) and the ILAE Classification of Epilepsies and Epileptic Syndromes (1989). Diagnosis should have been established by clinical history, electroencephalogram (EEG) and computed tomography/magnetic resonance imaging (CT/MRI) of the brain consistent with idiopathic generalised epilepsy. A CT/MRI scan should have been performed within five years of the screening visit or, if not available from this period, should be performed in the Baseline Period.
  6. EEG should have been performed within one year of the screening visit or, if not available from this period, should be performed in the Baseline Period.
  7. Female subjects are pre-menarchal, or if of childbearing potential, are not pregnant or lactating, or are post-menopausal.
  8. Female subjects of childbearing potential ≥ 18 years must abide by one of the following medically acceptable contraceptive measures: oral contraception pill, contraceptive injections, implants or patches, intrauterine device in place for at least three months or vasectomised partner or abstinence throughout the study. Subjects <18 years and of childbearing potential must be either abstinent or willing to use one of the medically appropriate forms of contraception for the duration of the study.

Exclusion Criteria:

  1. Subject has progressive or focal neurological disease (as determined by preexisting brain imaging such as CT or MRI performed maximally five years before the screening visit), or clinically significant organic disease.
  2. Subject has a history of, or results of clinical investigations (including EEG data) that are suggestive of, partial seizures as defined by the ILAE, including generalised tonic clonic seizures which are suspected to be secondarily generalised.
  3. Subjects with cryptogenic or symptomatic generalised epilepsy.
  4. Subjects with psychogenic seizures.
  5. Subject has a history of convulsive status epilepticus within a year of screening while complying with AEDs.
  6. Subject has a history of renal calculi or renal insufficiency (above the upper normal limits of creatinine).
  7. Subject has a known diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C.
  8. Subject has a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
  9. Subject has a history of sensitivity to sulfonamide drugs or to zonisamide or any of its excipients.
  10. Subject has a recent history of excessive alcohol use or drug abuse.
  11. Subject has a history of suicide attempt in the five years before the screening visit.
  12. Subject has abnormal screening laboratory values that are clinically significant.
  13. Subject has a history of demonstrated non-compliance with treatment, or the subject or parent/caregiver can be reasonably expected not to be compliant with study procedures or to complete the study.
  14. Subject has participated in a study of an investigational drug or device within 30 days prior to screening.
  15. Subject has received previous treatment with zonisamide.
  16. Subject is treated with ketogenic diet or vagus nerve stimulator.
  17. Subject has a history of necessary treatment with rescue benzodiazepines which is foreseen to continue during the study. Rescue benzodiazepines will not be allowed in this study (stable dosing with a benzodiazepine as (one of the) baseline anti-epileptic drug(s) is allowed).
  18. Concomitant use of acetazolamide, carbonic anhydrase inhibitors such as topiramate and drugs with anticholinergic activity.
  19. Current psychosis or moderate to severe depression, or use of anti-psychotic drugs, MAOIs, tricyclic antidepressants, benzodiazepine or barbiturate treatment for disorders other than epilepsy, and stimulants (amphetamine derivatives) within 28 days before the screening visit.
  20. Concomitant use of felbamate or use of felbamate within two months prior to Visit 1.
  21. Subject is unable to swallow capsules.
  22. Subject is not in general good health as determined by medical history, physical exam and screening laboratory results.
  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: NCT00693017

  Hide Study Locations
Locations
Australia, New South Wales
Strategic Health Evaluators Pty Ltd
Chatswood, New South Wales, Australia, 2067
The Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Austin Health
Heidelburg, Victoria, Australia, 3084
The Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Croatia
CH Split
Split, HR, Croatia, 10000
CH Sestre Milosrdnice University Hospita
Zagreb, HR, Croatia, 10000
UHC Zagreb
Zagreb, HR, Croatia, 10000
Czech Republic
Neurologicke oddeleni
Kralove, Czech Republic, 500 03
Private Neurologi Office
Kromeriz, Czech Republic, 767 01
Fakultni nemocnice Olomouc
Olomouc, Czech Republic, 775 20
Fakultni nemocnice s poliklinikou Ostrava
Ostrava, Czech Republic, 708 52
Fakultni nemocnice Plzen
Plzen, Czech Republic, 305 99
Nemocnice Na Homolce
Praha 5, Czech Republic, 150 30
Centrum neurologicke pece
Rychnov nad Kneznou, Czech Republic, 516 01
Estonia
Neurodiagnostica AP OY
Tallinn, Estonia, 11312
West-Tallinn Central Hospital
Tallinn, Estonia, 10611
Tartu University Hospital
Tartu, Estonia, 51014
Finland
Kuopio Epilepsy Center
Kuopio, Finland, SF-70211
Oulu University Central Hospital
Oulu, Finland, 90220
Germany
Institut fur Diagnostik der Epilepsien (IDE) gGmbH Epilepsie-Zentrum Berlin- Brandenburg.
Berlin, Germany, 10365
Neurochirurgische Klinik der Universitat Freiburg
Freiburg, Germany, 79106
Interdisziplinares Epilepsiezentrum am Klinikum der Philipps-Universitat Marburg
Marburg, Germany, 35039
Neurologische Gemeinschaftspraxis
Munchen, Germany, 80333
Universitatsklinikum Ulm
Ulm, Germany, 89081
Hungary
Bethesda Hospital for Children
Budapest, Hungary, 1146
Heim Pal Hospital
Budapest, Hungary, 1089
Szent Istvan Hospital
Budapest, Hungary, 1091
Orszagos Idegsebeszeti Tudomanyos Intezet
Budapest, Hungary, 1145
National Institute of Psychiatry and Neurology
Budapest, Hungary, 1021
Bekes County Pandy Kalman Hospital
Gyula, Hungary, 5703
Bacs-Kiskun County ONK Hospital
Kecskemet, Hungary, 6000
Vas County Markusovszky Hospital
Szombathely, Hungary, 9400
Veszprem County Csolnoky F. Hospital
Veszprem, Hungary, 8200
Lithuania
Kaunas Medical University Hospital
Kaunas, Lithuania, 50009
Neuromeda
Kaunas, Lithuania, 50185
Vilnius University Hospital Santariskiu klinikos
Vilnius, Lithuania, 8861
Poland
Niepubliczny ZOZ Kendron
Bialystok, Poland, 15-420
Wojewozki Szpital Specjalistyczny im. M. Kopernika
Gdansk, Poland, 80-803
Specjalistyczny Szpital Wieloprofilowy
Katowice, Poland, 40-635
Centrum Neurologii Klinicznej
Krakow, Poland, 31-530
Szpital im. M. Kopernika
Lodz, Poland, 93-513
Uniwersytet Medyczny
Poznan, Poland, 60-355
Romania
Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"
Bucharest, Romania, 041914
Spitalul Universitar de Urgenta Bucuresti
Bucharest, Romania, 050098
Centrul Medical Sana
Bucharest, Romania, 011025
Spitalul Clinic Judetean de Urgenta Cluj
Cluj-Napoca, Romania, 400006
Spitalul Clinic de Urgenta "Sfanta Treime"
Lasi, Romania, 700309
Spitalul Clinic Judetean de Urgenta "Sf Spiridon" Iasi
Lasi, Romania, 700111
Spitalul Clinic Judetean de Urgenta Tg Mures
Tg Mures, Romania, 540136
Russian Federation
GOU VPO Krasnoyarskaya State Medical Academy of Roszdrav
Krasnoyarsk, Russian Federation, 660022
GOU VPO Russian State Medical University of Roszdrav
Moscow, Russian Federation, 117997
GOU VPO Moscow State University of Medicine and Dentistry of Roszdra
Moscow, Russian Federation, 127473
FGU Moscow Research Institute of Psychiatry of Roszdrav
Moscow, Russian Federation, 107076
GUZ of Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
Moscow, Russian Federation, 119049
GOU VPO Novosibirsk State Medical University of Roszdrav
Novosibirsk, Russian Federation, 630091
GOU VPO Smolensk State Medical Academy of Roszdrav
Smolensk, Russian Federation, 214018
GOU VPO Smolensk State Medical Academy of Roszdrav
Smolensk, Russian Federation, 214019
GU St. Petersburg Research Institute of Psychoneurology Bekhtereva of Roszdrav
St. Petersburg, Russian Federation, 192019
St. Petersburg State Medical Pediatric Academy
St. Petersburg, Russian Federation, 194100
GOU VPO St. Petersburg State Medical University
St. Petersburg, Russian Federation, 197022
Yaroslavskaya State Medical Academy
Yaroslavl, Russian Federation, 150000
Serbia
Clinical Center of Serbia
Belgrade, Serbia, 11000
University Medical Center Zvezdara
Belgrade, Serbia, 11000
Clinical center Kragujevac
Kragujevac, Serbia, 34000
Clinical Center of NIS
Nis, Serbia, 18000
Ukraine
Tsentr Psihosomatychnoyi Patologiyi Dnipropetrovskoyi oblasnoyi klinichnoyi likarni imeni Mechnikova
Dnipropetrovsk, Ukraine, 49005
Derzhavna Ustanova Institut Nevrologiy
Kharkiv, Ukraine, 61068
Kyiv City Psychiatric Hospital #2, Poliklinichne Viddilenya
Kyiv, Ukraine, 2660
Miska Klinichna psihonevrologichna
Kyiv, Ukraine, 3080
Lvivskyiy oblasnyi Protyepileptuchnyy tsentr
Lviv, Ukraine, 7910
Odesskyy Derzhavnyy Medychnyy Universitet
Odesa, Ukraine, 65006
Vinnitskyy Natsionalnyy Medychnyy Universitet
Vinnitsa, Ukraine, 21005
Sponsors and Collaborators
Eisai Limited
Investigators
Study Director: Rob van Maanen, M.D. Eisai Limited
  More Information

No publications provided

Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT00693017     History of Changes
Other Study ID Numbers: E2090-E044-317, 2007-003556-10
Study First Received: June 3, 2008
Results First Received: August 13, 2012
Last Updated: June 26, 2014
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Epilepsies, Myoclonic
Epilepsy
Epilepsy, Generalized
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Zonisamide
Anticonvulsants
Antioxidants
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014