A double-blind, randomised, placebo-controlled, multicentre study to assess the efficacy and safety of adjunctive zonisamide in primary generalised tonic clonic seizures
- Conditions
- Primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsy (IGE)MedDRA version: 9.1Level: HLTClassification code 10018101Term: Generalised tonic-clonic seizures
- Registration Number
- EUCTR2007-003557-91-DE
- Lead Sponsor
- Eisai Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 154
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 IGE and may be accompanied by other primary generalised 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 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 which has PGTCS (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. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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 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 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, Monoamine oxidase inhibitors (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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is to assess the efficacy of adjunctive zonisamide in idiopathic generalised epilepsy (IGE) in reducing the frequency of tonic-clonic seizures in subjects with continuing primary generalised tonic clonic seizures (PGTCS) despite treatment with one or two other anti-epileptic drugs (AEDs).<br><br>;Secondary Objective: To assess the safety and tolerability of adjunctive zonisamide.;Primary end point(s): The primary efficacy parameter is the 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% (i.e. 28-day PGTC seizure frequency in period from Week 4 to the Week 16 visit compared to Week -8 to randomisation).
- Secondary Outcome Measures
Name Time Method