A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy

NCT00477295 | Completed Phase 3 Results

• 2 other identifiers: E2090-E044-3102006-000156-40
• Study Type: interventional
• Target: 583
• Locations: 17 countries
• Sites: 77

Brief Summary

This is a two-arm, randomized, double-blind, non-inferiority study using a flexible dosing regime to allow optimal zonisamide or carbamazepine therapy for individual subjects. Assessment of eligibility will take place at the Screening Visit. The subjects will be randomized to either the carbamazepine or zonisamide arm at the Randomization Visit (T1). T1 must occur as soon as possible (and at least within 14 days) of the Screening Visit in order to optimize subject care.

Conditions

Epilepsy

Keywords

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase

  A subject achieved a 26-week seizure-free period if they were free of all seizures, regardless of seizure type, for 26 weeks while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.

  Week 31 through Week 109

Secondary Outcomes (10)

• Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period

  Week 5 through Week 109

• Analysis of Time to Drop Out Due to an Adverse Event (AE)

  Week 1 through Week 109

• Analysis of Time to Drop Out Due to Lack of Efficacy

  Week 1 through Week 109

• Time to 6-months Seizure Freedom

  Week 5 through Week 83

• Time to 12-months Seizure Freedom

  Week 5 through Week 83

Study Arms (2)

Zonisamide

ACTIVE COMPARATOR

Drug: Zonisamide

Carbamazepine

ACTIVE COMPARATOR

Drug: Carbamazepine

Interventions

Zonisamide DRUG

Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.

Also known as: Zonegran

Zonisamide

Carbamazepine DRUG

Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.

Carbamazepine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 18 to 75 years of age inclusive.
• Subjects with untreated, newly diagnosed epilepsy having at least two well documented, unprovoked, clinically evaluated and classified partial seizures (with or without secondary generalization) or generalized tonic-clonic seizures (without clear focal origin) within 12 months of the Screening Visit, of which at least one seizure occurred within three months of the Screening Visit (\> one seizure within a 24 hour period will be counted as one seizure).
• Subjects will either have had no previous use of an AED, or treatment with one AED for a maximum duration of two weeks before the Randomization Visit (T1).
• Subjects have a documented electroencephalogram (EEG) within 12 months of the Screening Visit, compatible with localization-related epilepsy (to exclude primary generalized epilepsy).
• Subjects have a documented computed axial tomography (CAT) scan or magnetic resonance imaging (MRI) scan confirming the absence of a progressive neurological lesion within 12 months of the Screening Visit.
• Female subjects without childbearing potential (two years post-menopausal, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative pregnancy test at screening and randomization, must not be lactating and must be using a medically acceptable form of contraception, for the duration of the study and for one month following discontinuation of the study drug. Medically acceptable contraception is defined here as oral contraception pill with at least 50 micrograms ethinylestradiol per intake, contraceptive injections and implants, or intrauterine device in place for at least three months.
• Subjects who are able and willing to follow investigational study procedures, maintain a seizure diary, and report AEs.
• Subjects who are able and willing to give written informed consent.

You may not qualify if:

• Subjects have a history of clinical investigations, including EEG data, that are suggestive of idiopathic generalised epilepsy as defined by the International League Against Epilepsy (ILAE).
• Subjects with a history of absence, myoclonic, clonic, tonic, or atonic seizures.
• Subjects have a history of status epilepticus, and/or non-epileptic seizures (e.g., metabolic, pseudo-seizures).
• Subjects have experienced seizures relating to drugs, alcohol, acute medical illness, mental retardation, or subjects with situation-related seizures.
• Subjects have progressive encephalopathy or findings consistent with progressive CNS disease or lesion (e.g. infection, demyelination, or tumour).
• Subjects have a history of a significant or currently uncontrolled disease that will interfere with the conduct of this study or the assessment of safety and efficacy of the study drug.
• Subjects have been previously treated with carbamazepine or zonisamide.
• Subjects have received an investigational drug or device in the three months prior to the Screening Visit.
• Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, or tricyclic antidepressants.
• Subjects have a history of bone marrow depression, low platelet count or other blood dyscrasia.
• Subjects have a history of acute intermittent porphyria.
• Subjects have a history of renal disorder (serum creatinine level of \> 135 ìmol / l (1.5 mg/dL at the Screening Visit), hepatic disorder or clinically significant abnormal liver function tests; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2 times the upper normal limit.
• Subjects have a body weight of less than 40 kg.
• Subjects have a history of progressive malignancy within the previous 5 years (excluding a history of non-metastasized and adequately treated cutaneous squamous cell carcinoma).
• Subjects have a history of psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months which is considered uncontrolled; a history of suicide attempt; alcohol or drug abuse; chronic treatment with benzodiazepines or barbiturates.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (79)

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Camperdown, Australia

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Clayton, Australia

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Fitzroy, Australia

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Flinders, Australia

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Heidelberg West, Australia

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Parkville, Australia

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Queensland, Australia

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Wellington, Australia

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Aalborg, Denmark

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Béthune, France

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Dijon, France

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Paris, France

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Saint-Etienne, France

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Berlin, Germany

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Bochum, Germany

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Düsseldorf, Germany

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Munich, Germany

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Schwerin, Germany

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Westerstede, Germany

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Athens, Greece

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Thessaloniki, Greece

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Budapest, Hungary

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Debrecen, Hungary

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Gyula, Hungary

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Hódmezővásárhely, Hungary

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Nyregyhaza, Hungary

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Zalaegerszeg-Pozva, Hungary

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Bangalore, India

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Hyderabad, India

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Koturpuram, India

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Madurai, India

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New Delhi, India

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Pune, India

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Milan, Italy

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Monza, Italy

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Orbassano, Italy

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Rome, Italy

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Gdansk, Poland

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Katowice, Poland

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Krakow, Poland

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Lodz, Poland

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Lublin, Poland

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Poznan, Poland

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Sosnowiec, Poland

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Szcecin, Poland

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Warsaw, Poland

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Kaliningrad, Russia

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Kazan', Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Yaroslavl, Russia

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Belgrade, Serbia

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Niš, Serbia

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Novi Sad, Serbia

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Subotica, Serbia

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Bratislava, Slovakia

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Bratslava, Slovakia

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Brezno, Slovakia

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Nové Zámky, Slovakia

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Vranov nad Topľou, Slovakia

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Žilina, Slovakia

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Sandton, South Africa

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Anyang, South Korea

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Seoul, South Korea

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Wŏnju, South Korea

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Alicante, Spain

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Bacelona, Spain

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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Oviedo, Spain

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Seville, Spain

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Gothenburg, Sweden

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Lund, Sweden

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Changhua, Taiwan

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Yongkang District, Taiwan

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Bristol, United Kingdom

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Liverpool, United Kingdom

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Treliske, United Kingdom

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Related Publications (1)

• Baulac M, Brodie MJ, Patten A, Segieth J, Giorgi L. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol. 2012 Jul;11(7):579-88. doi: 10.1016/S1474-4422(12)70105-9. Epub 2012 Jun 8.

  PMID: 22683226 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

Zonisamide; Carbamazepine

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; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Joanna Segieth

  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: May 21, 2007
• First Posted: May 23, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: December 24, 2015
• Results First Posted: February 8, 2013

Record last verified: 2015-11

Locations

RU (5); ES (7); IN (6); FR (4); DK (1); AU (8); SL (6); KR (3); DE (6); IT (4); HU (6); SE (4); GB (3); GR (2); TW (2); PL (9); ZA (1)