Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures

NCT ID: NCT00692003

Last Updated: 2017-03-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-01
• Study Completion Date: 2009-01-09

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).

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Zonisamide

Group Type: ACTIVE_COMPARATOR

Zonisamide

Intervention Type: DRUG

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)

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Zonegran

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rob Van Maanen

Role: STUDY_DIRECTOR

Eisai Limited

Locations

Strategic Health Evaluators Pty Ltd

Chatswood, New South Wales, Australia

The Prince of Wales Hospital

Randwick, New South Wales, Australia

Austin Health

Heidelburg, Victoria, Australia

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

St. Vincents Hospital

Melbourne, , Australia

CH Split

Split, HR, Croatia

CH Sestre Milosrdnice University Hospital

Zagreb, HR, Croatia

UHC Zagreb

Zagreb, HR, Croatia

Neurologicke oddeleni

Hradec Králové, , Czechia

Private Neurologi Office

Kroměříž, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Fakultni nemocnice s poliklinikou Ostrava

Ostrava, , Czechia

Fakultni nemocnice Plzen

Pilsen, , Czechia

Nemocnice Na Homolce

Prague, , Czechia

Centrum neurologicke pece

Rychnov nad Kněžnou, , Czechia

West-Tallinn Central Hospital

Tallinn, , Estonia

Neurodiagnostica AP OY

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Kuopio Epilepsy Center

Kuopio, SF, Finland

Oulu University Central Hospital

Oulu, , Finland

Institut fur Diagnostik der Epilepsien

Berlin, , Germany

Neurochirurgische Klinik der Universitat Freiburg

Freiburg im Breisgau, , Germany

Interdisziplinares Epilepsiezentrum am Klinikum der Philipps-Universitat Marburg

Marburg, , Germany

Neurologische Gemeinschaftspraxis

München, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

National Institute of Psychiatry and Neurology

Budapest, , Hungary

Heim Pal Hospital

Budapest, , Hungary

Szent Istvan Hospital

Budapest, , Hungary

Orszagos Idegsebeszeti Tudomanyos Intezet

Budapest, , Hungary

Bethesda Hospital for Children

Budapest, , Hungary

Bekes County Pandy Kalman Hospital

Gyula, , Hungary

Bacs-Kiskun County ONK Hospital

Kecskemét, , Hungary

Vas County Markusovszky Hospital

Szombathely, , Hungary

Veszpem County Csolnoky F. Hospital

Veszpem, , Hungary

Kaunas Medical University Hospital

Kaunas, , Lithuania

Neuromeda

Kaunas, , Lithuania

Vilnius University Hospital Santariskiu klinikos

Vilnius, , Lithuania

Niepubliczny ZOZ KENDRON

Bialystok, , Poland

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Gdansk, , Poland

Specjalistyczny Szpital Wieloprofilowy

Katowice, , Poland

Centrum Neurologii Klinicznej

Krakow, , Poland

Szpital im. M. Kopernika

Lodz, , Poland

Uniwersytet Medyczny

Poznan, , Poland

Spitalul Clinic de Psihiatrie

Bucharest, , Romania

Spitalul Universitar de Urgenta Bucuresti

Bucharest, , Romania

Centrul Medical Sana

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, , Romania

Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi

Iași, , Romania

Spitalul Clinic de Urgenta Sfanta Treime

Iași, , Romania

Spitalul Clinic Judetean de Urgenta Tg Mures

Tg Mures, , Romania

GOU VPO Krasnoyarskaya State Medical Academy of Roszdrav

Krasnoyarsk, , Russia

FGU Moscow Research Institute of Psychiatry of Roszdrav

Moscow, , Russia

GOU VPO Russian State Medical University of Roszdrav

Moscow, , Russia

GOU VPO Smolensk State Medical Academy of Roszdrav

Moscow, , Russia

GOU VPO Moscow State University of Medicine and Dentistry of Roszdrav

Moscow, , Russia

GOU VPO Novosibirsk State Medical University of Roszdrav

Novosibirsk, , Russia

GU St. Petersburg Research Institute of Psychoneurology

Saint Petersburg, , Russia

St. Petersburg State Medical Pediatric Academy

Saint Petersburg, , Russia

GOU VPO St. Petersburg State Medical University

Saint Petersburg, , Russia

GOU VPO Smolensk State Medical Academy of Roszdrav

Smolensk, , Russia

GOU VPO Smolensk State Medical Academy of Roszdrav

Smolensk, , Russia

Yaroslavskaya State Medical Academy

Yaroslavl, , Russia

Clinical Center of Serbia

Belgrade, , Serbia

University Medical Center Zvezdara

Belgrade, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center of Nis

Niš, , Serbia

Tsentr Psihosomatychnoyi Patologiyi Dnipropetrovskoyi oblasnoyi klinichnoyi likarni imeni Mechnikova

Dniepropetrovsk, , Ukraine

Derzhavna Ustanova Institut Nevrologiy

Kharkiv, , Ukraine

Kyiv City Psychiatric Hospital #2, Poliklinichne Viddilenya

Kyiv, , Ukraine

Miska Klinichna psihonevrologichna Tsentr Epilepsiyi

Kyiv, , Ukraine

Lvivskyiy oblasnyi Protyepileptuchnyy tsentr

Lviv, , Ukraine

Odesskyy Derzhavnyy Medychnyy Universitet

Odesa, , Ukraine

Vinnitskyy Natsionalnyy Medychnyy Universitet

Vinnitsa, , Ukraine

Countries

Australia; Croatia; Czechia; Estonia; Finland; Germany; Hungary; Lithuania; Poland; Romania; Russia; Serbia; Ukraine

Other Identifiers

Eudra ID #2007-003557-91.

Identifier Type: -

Identifier Source: secondary_id

E2090-E044-315

Identifier Type: -

Identifier Source: org_study_id