Clinical trial NCT00692003: Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Official title: A Double-blind, Randomised, Placebo-controlled Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-06
Enrollment: 21
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Considered Responders as Assessed During the Maintenance Period
timeFrame: Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16)
Secondary outcomes:
measure: Absolute Change From Baseline in 28-day PGTC Seizure Frequency
timeFrame: Baseline and up to 16 weeks
Other outcomes:
Locations:
city: Chatswood
country: Australia
facility: Strategic Health Evaluators Pty Ltd
state: New South Wales
city: Randwick
country: Australia
facility: The Prince of Wales Hospital
state: New South Wales
city: Heidelburg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St. Vincents Hospital
city: Split
country: Croatia
facility: CH Split
state: HR
city: Zagreb
country: Croatia
facility: CH Sestre Milosrdnice University Hospital
state: HR
city: Zagreb
country: Croatia
facility: UHC Zagreb
state: HR
city: Hradec Kralove
country: Czech Republic
facility: Neurologicke oddeleni
city: Kromeriz
country: Czech Republic
facility: Private Neurologi Office
city: Olomouc
country: Czech Republic
facility: Fakultni nemocnice Olomouc
city: Ostrava
country: Czech Republic
facility: Fakultni nemocnice s poliklinikou Ostrava
city: Plzen
country: Czech Republic
facility: Fakultni nemocnice Plzen
city: Praha 5
country: Czech Republic
facility: Nemocnice Na Homolce
city: Rychnov nad Kneznou
country: Czech Republic
facility: Centrum neurologicke pece
city: Tallinn
country: Estonia
facility: West-Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: Neurodiagnostica AP OY
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Kuopio
country: Finland
facility: Kuopio Epilepsy Center
state: SF
city: Oulu
country: Finland
facility: Oulu University Central Hospital
city: Berlin
country: Germany
facility: Institut fur Diagnostik der Epilepsien
city: Freiburg
country: Germany
facility: Neurochirurgische Klinik der Universitat Freiburg
city: Marburg
country: Germany
facility: Interdisziplinares Epilepsiezentrum am Klinikum der Philipps-Universitat Marburg
city: Munchen
country: Germany
facility: Neurologische Gemeinschaftspraxis
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Budapest
country: Hungary
facility: National Institute of Psychiatry and Neurology
city: Budapest
country: Hungary
facility: Heim Pal Hospital
city: Budapest
country: Hungary
facility: Szent Istvan Hospital
city: Budapest
country: Hungary
facility: Orszagos Idegsebeszeti Tudomanyos Intezet
city: Budapest
country: Hungary
facility: Bethesda Hospital for Children
city: Gyula
country: Hungary
facility: Bekes County Pandy Kalman Hospital
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun County ONK Hospital
city: Szombathely
country: Hungary
facility: Vas County Markusovszky Hospital
city: Veszpem
country: Hungary
facility: Veszpem County Csolnoky F. Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital
city: Kaunas
country: Lithuania
facility: Neuromeda
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu klinikos
city: Bialystok
country: Poland
facility: Niepubliczny ZOZ KENDRON
city: Gdansk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika
city: Katowice
country: Poland
facility: Specjalistyczny Szpital Wieloprofilowy
city: Krakow
country: Poland
facility: Centrum Neurologii Klinicznej
city: Lodz
country: Poland
facility: Szpital im. M. Kopernika
city: Poznan
country: Poland
facility: Uniwersytet Medyczny
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie
city: Bucharest
country: Romania
facility: Spitalul Universitar de Urgenta Bucuresti
city: Bucharest
country: Romania
facility: Centrul Medical Sana
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj
city: Iasi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi
city: Iasi
country: Romania
facility: Spitalul Clinic de Urgenta Sfanta Treime
city: Tg Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Tg Mures
city: Krasnoyarsk
country: Russian Federation
facility: GOU VPO Krasnoyarskaya State Medical Academy of Roszdrav
city: Moscow
country: Russian Federation
facility: FGU Moscow Research Institute of Psychiatry of Roszdrav
city: Moscow
country: Russian Federation
facility: GOU VPO Russian State Medical University of Roszdrav
city: Moscow
country: Russian Federation
facility: GOU VPO Smolensk State Medical Academy of Roszdrav
city: Moscow
country: Russian Federation
facility: GOU VPO Moscow State University of Medicine and Dentistry of Roszdrav
city: Novosibirsk
country: Russian Federation
facility: GOU VPO Novosibirsk State Medical University of Roszdrav
city: Smolensk
country: Russian Federation
facility: GOU VPO Smolensk State Medical Academy of Roszdrav
city: Smolensk
country: Russian Federation
facility: GOU VPO Smolensk State Medical Academy of Roszdrav
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical Pediatric Academy
city: St.Petersburg
country: Russian Federation
facility: GU St. Petersburg Research Institute of Psychoneurology
city: St.Petersburg
country: Russian Federation
facility: GOU VPO St. Petersburg State Medical University
city: Yaroslavl
country: Russian Federation
facility: Yaroslavskaya State Medical Academy
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: University Medical Center Zvezdara
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Nis
country: Serbia
facility: Clinical Center of Nis
city: Dniepropetrovsk
country: Ukraine
facility: Tsentr Psihosomatychnoyi Patologiyi Dnipropetrovskoyi oblasnoyi klinichnoyi likarni imeni Mechnikova
city: Kharkiv
country: Ukraine
facility: Derzhavna Ustanova Institut Nevrologiy
city: Kyiv
country: Ukraine
facility: Kyiv City Psychiatric Hospital #2, Poliklinichne Viddilenya
city: Kyiv
country: Ukraine
facility: Miska Klinichna psihonevrologichna Tsentr Epilepsiyi
city: Lviv
country: Ukraine
facility: Lvivskyiy oblasnyi Protyepileptuchnyy tsentr
city: Odesa
country: Ukraine
facility: Odesskyy Derzhavnyy Medychnyy Universitet
city: Vinnitsa
country: Ukraine
facility: Vinnitskyy Natsionalnyy Medychnyy Universitet
Study officials:
affiliation: Eisai Limited
name: Rob Van Maanen
role: STUDY_DIRECTOR
References: