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

June 3, 2008
June 26, 2014
June 2008
November 2008   (final data collection date for primary outcome measure)
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.
Proportion of responders as assessed during the maintenance phase. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00693017 on ClinicalTrials.gov Archive Site
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.
Percentage change from baseline in the monthly number of days with myoclonic seizures; AEs, SAEs; incidence of Treatment Emergent Adverse Events (TEAEs); physical and neurological examinations; vital signs; clinical lab tests; weight, height; ECGs. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy
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

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).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Epilepsy
  • 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
  • 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)

  • Active Comparator: Zonisamide
    Intervention: Drug: Zonisamide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
10
Not Provided
November 2008   (final data collection date for primary outcome measure)

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.
Both
12 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Croatia,   Czech Republic,   Estonia,   Finland,   Germany,   Hungary,   Lithuania,   Poland,   Romania,   Russian Federation,   Serbia,   Ukraine
 
NCT00693017
E2090-E044-317, 2007-003556-10
Not Provided
Eisai Inc. ( Eisai Limited )
Eisai Limited
Not Provided
Study Director: Rob van Maanen, M.D. Eisai Limited
Eisai Inc.
June 2012

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