Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures

NCT00692003 | Terminated Phase 3 Results

• 2 other identifiers: E2090-E044-315Eudra ID #2007-003557-91.
• Study Type: interventional
• Target: 21
• Locations: 13 countries
• Sites: 73

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Considered Responders as Assessed During the Maintenance Period

  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.

  Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16)

Secondary Outcomes (1)

• Absolute Change From Baseline in 28-day PGTC Seizure Frequency

  Baseline and up to 16 weeks

Study Arms (2)

Zonisamide

ACTIVE COMPARATOR

Drug: Zonisamide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Zonisamide 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)

Also known as: Zonegran

Zonisamide

Placebo 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)

Placebo

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is male or female and aged 6-65 years.
• 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.
• 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.
• 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).
• 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.
• 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.
• Female subjects are pre-menarchal, or if of childbearing potential, are not pregnant or lactating or are post-menopausal.
• 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.
• Subject has a body weight ≥ 20 kg.

You may not qualify if:

• 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.
• 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.
• Subjects with cryptogenic or symptomatic generalized epilepsy.
• Subjects with psychogenic seizures.
• Subject has a history of status epilepticus within a year of screening while complying with AEDs.
• Subject has seizures that only occur in clustered patterns.
• Subject has a history of renal calculi or renal insufficiency (above the upper normal limits of creatinine).
• Subject has a known diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C.
• Subject had a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
• Subject has a history of sensitivity to sulfonamide drugs or zonisamide and its excipients.
• Subject has a recent history of excessive alcohol use or drug abuse.
• Subject has a history of suicide attempt in the five years before the screening visit..
• Subject has abnormal screening laboratory values that were clinically significant.
• 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.
• Subject has participated in a study of an investigational drug or device within 30 days prior to screening.

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (73)

Strategic Health Evaluators Pty Ltd

Chatswood, New South Wales, 2067, Australia

Location

The Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Austin Health

Heidelburg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

St. Vincents Hospital

Melbourne, Australia

Location

CH Split

Split, HR, 10000, Croatia

Location

CH Sestre Milosrdnice University Hospital

Zagreb, HR, 10000, Croatia

Location

UHC Zagreb

Zagreb, HR, 10000, Croatia

Location

Neurologicke oddeleni

Hradec Králové, 500 03, Czechia

Location

Private Neurologi Office

Kroměříž, 767 01, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Fakultni nemocnice s poliklinikou Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni nemocnice Plzen

Pilsen, 305 99, Czechia

Location

Nemocnice Na Homolce

Prague, 150 30, Czechia

Location

Centrum neurologicke pece

Rychnov nad Kněžnou, 516 01, Czechia

Location

West-Tallinn Central Hospital

Tallinn, 10611, Estonia

Location

Neurodiagnostica AP OY

Tallinn, 11312, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Kuopio Epilepsy Center

Kuopio, SF, 70211, Finland

Location

Oulu University Central Hospital

Oulu, 90220, Finland

Location

Institut fur Diagnostik der Epilepsien

Berlin, 10365, Germany

Location

Neurochirurgische Klinik der Universitat Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Interdisziplinares Epilepsiezentrum am Klinikum der Philipps-Universitat Marburg

Marburg, 35039, Germany

Location

Neurologische Gemeinschaftspraxis

München, 80333, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

National Institute of Psychiatry and Neurology

Budapest, 1021, Hungary

Location

Heim Pal Hospital

Budapest, 1089, Hungary

Location

Szent Istvan Hospital

Budapest, 1091, Hungary

Location

Orszagos Idegsebeszeti Tudomanyos Intezet

Budapest, 1145, Hungary

Location

Bethesda Hospital for Children

Budapest, 1146, Hungary

Location

Bekes County Pandy Kalman Hospital

Gyula, 5703, Hungary

Location

Bacs-Kiskun County ONK Hospital

Kecskemét, 6000, Hungary

Location

Vas County Markusovszky Hospital

Szombathely, 9400, Hungary

Location

Veszpem County Csolnoky F. Hospital

Veszpem, 8200, Hungary

Location

Kaunas Medical University Hospital

Kaunas, 50009, Lithuania

Location

Neuromeda

Kaunas, 50185, Lithuania

Location

Vilnius University Hospital Santariskiu klinikos

Vilnius, 8661, Lithuania

Location

Niepubliczny ZOZ KENDRON

Bialystok, 15-420, Poland

Location

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Gdansk, 80-803, Poland

Location

Specjalistyczny Szpital Wieloprofilowy

Katowice, 40-635, Poland

Location

Centrum Neurologii Klinicznej

Krakow, 31-530, Poland

Location

Szpital im. M. Kopernika

Lodz, 93-513, Poland

Location

Uniwersytet Medyczny

Poznan, 60-355, Poland

Location

Spitalul Clinic de Psihiatrie

Bucharest, 041914, Romania

Location

Spitalul Universitar de Urgenta Bucuresti

Bucharest, 050098, Romania

Location

Centrul Medical Sana

Bucharest, 11025, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, 400006, Romania

Location

Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi

Iași, 700111, Romania

Location

Spitalul Clinic de Urgenta Sfanta Treime

Iași, 700309, Romania

Location

Spitalul Clinic Judetean de Urgenta Tg Mures

Tg Mures, 540136, Romania

Location

GOU VPO Krasnoyarskaya State Medical Academy of Roszdrav

Krasnoyarsk, 660022, Russia

Location

FGU Moscow Research Institute of Psychiatry of Roszdrav

Moscow, 107076, Russia

Location

GOU VPO Russian State Medical University of Roszdrav

Moscow, 117997/119034, Russia

Location

GOU VPO Smolensk State Medical Academy of Roszdrav

Moscow, 119049, Russia

Location

GOU VPO Moscow State University of Medicine and Dentistry of Roszdrav

Moscow, 127473 / 107006, Russia

Location

GOU VPO Novosibirsk State Medical University of Roszdrav

Novosibirsk, 630091, Russia

Location

GU St. Petersburg Research Institute of Psychoneurology

Saint Petersburg, 192019, Russia

Location

St. Petersburg State Medical Pediatric Academy

Saint Petersburg, 194100, Russia

Location

GOU VPO St. Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

GOU VPO Smolensk State Medical Academy of Roszdrav

Smolensk, 214018, Russia

Location

GOU VPO Smolensk State Medical Academy of Roszdrav

Smolensk, 214019, Russia

Location

Yaroslavskaya State Medical Academy

Yaroslavl, 150000, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

University Medical Center Zvezdara

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center of Nis

Niš, 18000, Serbia

Location

Tsentr Psihosomatychnoyi Patologiyi Dnipropetrovskoyi oblasnoyi klinichnoyi likarni imeni Mechnikova

Dniepropetrovsk, 49005, Ukraine

Location

Derzhavna Ustanova Institut Nevrologiy

Kharkiv, 61068, Ukraine

Location

Kyiv City Psychiatric Hospital #2, Poliklinichne Viddilenya

Kyiv, 2660, Ukraine

Location

Miska Klinichna psihonevrologichna Tsentr Epilepsiyi

Kyiv, 3080, Ukraine

Location

Lvivskyiy oblasnyi Protyepileptuchnyy tsentr

Lviv, 7910, Ukraine

Location

Odesskyy Derzhavnyy Medychnyy Universitet

Odesa, 65006, Ukraine

Location

Vinnitskyy Natsionalnyy Medychnyy Universitet

Vinnitsa, 21005, Ukraine

Location

MeSH Terms

Conditions

Epilepsy

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was terminated early at the Sponsor's discretion. When this study was discontinued, only 6 subjects had been treated. Data from the 5 subjects treated with zonisamide were insufficient to draw firm conclusions regarding efficacy.

Results Point of Contact

• Title: Antonio Laurenza, MD, Executive Director
• Organization: Eisai Inc

antonio_laurenza@eisai.com

1 201 949-4157

Study Officials

• Rob Van Maanen

  Eisai Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 6, 2008
• Study Start: August 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: January 9, 2009
• Last Updated: March 14, 2017
• Results First Posted: October 12, 2012

Record last verified: 2017-02

Locations

SE (4); LI (3); PL (6); UA (7); HU (9); FI (2); AU (5); RO (7); RU (12); CR (3); CZ (7); DE (5); ES (3)