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Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00692003
Recruitment Status : Terminated (Sponsor's decision)
First Posted : June 6, 2008
Results First Posted : October 12, 2012
Last Update Posted : March 14, 2017
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )

Tracking Information
First Submitted Date  ICMJE June 3, 2008
First Posted Date  ICMJE June 6, 2008
Results First Submitted Date  ICMJE August 13, 2012
Results First Posted Date  ICMJE October 12, 2012
Last Update Posted Date March 14, 2017
Actual Study Start Date  ICMJE August 1, 2008
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
Number of Participants Considered Responders as Assessed During the Maintenance Period [ Time Frame: Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16) ]
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 from baseline in Primary Generalised Tonic-Clonic Seizures (PGTCS) frequency of >= 50% (i.e. 28-day PGTC seizure frequency in the period from Week 4 to the Week 16 visit compared to Week -8/-4 to randomization at Week 0). Each participant's response to treatment was assessed on the basis of their seizure diaries. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) through out the titration and maintenance treatment periods until the Early termination Visit at Week 16. Due to early termination of the study by the Sponsor, no formal analyses were conducted.
Original Primary Outcome Measures  ICMJE
 (submitted: June 5, 2008)
Proportion of responders assessed during the maintenance phase. A responder is defined as a subject with a decrease from baseline in PGTCS frequency of = 50%. [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
Absolute Change From Baseline in 28-day PGTC Seizure Frequency [ Time Frame: Baseline and up to 16 weeks ]
Absolute Change from Baseline in 28-day PGTC Seizure Frequency 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2008)
The absolute change from baseline in 28 day PGTC seizure frequency. [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Official Title  ICMJE A Double-blind, Randomised, Placebo-controlled Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Brief Summary Zonisamide is already marketed for the treatment of partial seizures in epilepsy. This study is intended to provide evidence that zonisamide is safe and effective in the treatment of primary generalised tonic-clonic seizures. The total trial duration will be 5.5-6.5 months. After that subjects who have completed the study will be eligible to enrol 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-E044-316).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE
  • Drug: Zonisamide

    25-400 mg capsules orally once daily in the evening.

    Maximum study duration of 28 weeks comprising:

    Baseline Period (Week-8/-4 to Week 0) no treatment

    Titration Period (Week 0 to Week 4) <12 years old: 1 mg/kg; >= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4

    Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)

    Down Titration Period (4 weeks)

    Other Name: Zonegran
  • Drug: Placebo

    25-400 mg Zonisamide Placebo capsules orally once daily in the evening.

    Maximum study duration of 28 weeks comprising:

    Baseline Period (Week-8/-4 to Week 0) no treatment

    Titration Period (Week 0 to Week 4) <12 years old: 1 mg/kg Zonisamide Placebo; >= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4

    Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)

    Down Titration Period (4 weeks)

Study Arms  ICMJE
  • Active Comparator: Zonisamide
    Intervention: Drug: Zonisamide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 11, 2012)
21
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2008)
154
Actual Study Completion Date  ICMJE January 9, 2009
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject is male or female and aged 6-65 years.
  2. Subject has ≥ 3 PGTCS over the two months before screening and during the eight weeks Baseline Period with at least one seizure in each one month period. PGTCS must occur in the context of Idiopathic Generalized Epilepsy (IGE) and may be accompanied by other primary generalized seizures, provided these are also consistent with a diagnosis of IGE.
  3. Subject (or parent/caregiver, for subjects below the age of consent) is willing to sign an informed consent form. For subjects below the age of consent in their country, where appropriate they must 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 Antiepileptic Drugs (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 generalized epilepsy which has PGTCS (and which may be accompanied by other generalized 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 generalized epilepsy. 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 must abide by the 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.
  9. Subject has a body weight ≥ 20 kg.

Exclusion Criteria:

  1. Subject has progressive or focal neurological disease (as determined by pre-existing 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 generalized tonic clonic seizures which are suspected to be secondarily generalized.
  3. Subjects with cryptogenic or symptomatic generalized epilepsy.
  4. Subjects with psychogenic seizures.
  5. Subject has a history of status epilepticus within a year of screening while complying with AEDs.
  6. Subject has seizures that only occur in clustered patterns.
  7. Subject has a history of renal calculi or renal insufficiency (above the upper normal limits of creatinine).
  8. Subject has a known diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C.
  9. Subject had a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
  10. Subject has a history of sensitivity to sulfonamide drugs or zonisamide and its excipients.
  11. Subject has a recent history of excessive alcohol use or drug abuse.
  12. Subject has a history of suicide attempt in the five years before the screening visit..
  13. Subject has abnormal screening laboratory values that were clinically significant.
  14. 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.
  15. Subject has participated in a study of an investigational drug or device within 30 days prior to screening.
  16. Subject has received previous treatment with zonisamide.
  17. Subject is treated with ketogenic diet or vagus nerve stimulator.
  18. 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).
  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 acetazolamide, carbonic anhydrase inhibitors such as topiramate and drugs with anticholinergic activity.
  21. Concomitant use of felbamate or use of felbamate within two months prior to Visit 1.
  22. Subject is not able to swallow capsules.
  23. Subject is not in general good health as determined by medical history, physical exam and screening laboratory results.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Croatia,   Czech Republic,   Estonia,   Finland,   Germany,   Hungary,   Lithuania,   Poland,   Romania,   Russian Federation,   Serbia,   Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00692003
Other Study ID Numbers  ICMJE E2090-E044-315
Eudra ID #2007-003557-91.
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc. ( Eisai Limited )
Study Sponsor  ICMJE Eisai Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Rob Van Maanen Eisai Limited
PRS Account Eisai Inc.
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP