Assessing The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures

NCT00848549 | Completed Phase 3 Results

• 2 other identifiers: E2090-E044-3142008-001159-23
• Study Type: interventional
• Target: 295
• Locations: 19 countries
• Sites: 130

Brief Summary

The purpose of this study is to assess the long-term safety and tolerability and to explore the long-term efficacy of zonisamide as monotherapy treatment in subjects with newly diagnosed partial seizures.

Conditions

Epilepsy

Keywords

Epilepsy; Monotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Remaining in the Study at Each Visit

  The retention rate is defined as the percentage of subjects remaining on the study at each visit, starting from the first dose of study drug in the extension phase.

  At 3, 6, 9, 12, 15, 18, 21, 24, and 27 months

Secondary Outcomes (4)

• Time to Drop-out Due to Lack of Efficacy

  Week 1 to Week 109 (in core study) and Month 1 to Month 27 (in extension study)

• Time to Drop-out Due to Adverse Event (AE)

  Week 1 to Week 109 (in base study) and Month 1 to Month 27 (in extension study)

• Percentage of Participants That Are Seizure Free for at Least 24 Month Consecutive Period in the Base Study and Extension Phase

  Week 5 to Week 109 (in base study) and Month 1 to Month 27 (in extension phase)

• Change From Baseline in Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) Overall Score at Each Visit

  Weeks 0, 26, 52, 78 and 117

Study Arms (2)

ZNS

ACTIVE COMPARATOR

Drug: Zonisamide

CBZ

ACTIVE COMPARATOR

Drug: Carbamazepine

Interventions

Zonisamide DRUG

Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 500 mg; the minimum daily dose allowable is 200 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events, respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 100 mg per week.

Also known as: Zonegran

ZNS

Carbamazepine DRUG

Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 1200 mg; the minimum daily dose allowable is 400 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 200 mg per week.

CBZ

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has completed study E2090-E044-310.
• Subject is able and willing to give written informed consent.
• Female subjects without childbearing potential (two years post-menopausal, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects of childbearing potential must be non-pregnant, non-lactating and abide by one of the following medically acceptable contraceptive measures: oral contraceptive pill, contraceptive injections, implants or patches, intrauterine device in place for at least three months, vasectomised partner or abstinence throughout the study and for one month after discontinuation of study medication. When the contraceptive pill is used, this should contain no less than 50 μg oestrogen.
• The subject is able and willing to follow the investigational study procedures, maintain a seizure diary and report adverse events.

You may not qualify if:

• Subject has a history of a significant or currently uncontrolled disease that will contraindicate the use of the study drugs or interfere with the conduct of this study and/or the assessment of safety and efficacy of the study drugs.
• Subject has a body weight \<40 kg.
• Subject has a newly occurring progressive malignancy during study E2090-E044-310 (excluding a history of non-metastasized and adequately treated cutaneous squamous cell carcinoma).
• Subject has developed a psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months and is considered uncontrolled; history of suicide attempt, alcohol or drug abuse, chronic treatment with benzodiazepines or barbiturates.
• Subject is currently taking carbonic anhydrase inhibitors.
• Subject developed pancreatitis, nephrolithiasis or hypercalcuria, clinically significant laboratory abnormalities, stroke or uncontrolled hypertension during study E2090-E044-310.
• Subject is currently taking monoamine oxidase inhibitors (MAOIs) or any other excluded medications (see protocol section 9.9.3).
• Subject has a history of allergy to carbamazepine or to zonisamide or to any of their ingredients or to sulphonamides.
• Subject has developed a bone marrow depression, low platelet count or other blood dyscrasias.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (133)

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Camperdown, New South Wales, 2050, Australia

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Bedford Park, South Australia, 5042, Australia

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Clayton, Victoria, 3168, Australia

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Fitzroy, Victoria, 3065, Australia

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Heidelberg West, Victoria, 3084, Australia

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Parkville, Victoria, 3050, Australia

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Perth, Western Australia, 6000, Australia

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Queensland, 4558, Australia

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Aalborg, 9000, Denmark

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Béthune, 62408, France

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Dijon, 21033, France

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Paris, 75651, France

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Saint-Etienne, 42055, France

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Berlin, 13353, Germany

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Bochum, 44805, Germany

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Düsseldorf, 40212, Germany

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Munich, 81377, Germany

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Schwerin, 19053, Germany

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Westerstede, 26676, Germany

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Athens, 10676, Greece

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Athens, 11525, Greece

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Athens, 15562, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 54636, Greece

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Thessaloniki, 55236, Greece

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Thessaloniki, 57010, Greece

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Budapest, 1076, Hungary

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Budapest, 1096, Hungary

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Budapest, 1145, Hungary

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Debrecen, 4032, Hungary

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Gyula, 5700, Hungary

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Hódmezővásárhely, 6800, Hungary

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Nyregyhaza, 4400, Hungary

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Zalaegerszeg-Poozva, 8908, Hungary

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Bangalore, 560034, India

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Bangalore, 560094, India

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Hyderabad, 500 001, India

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Koturpuram, Chennai, 600 085, India

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Madurai, Tamil Nadu, 625 020, India

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Mumbai, 400 012, India

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New Delhi, 110 016, India

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New Delhi, 110 065, India

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New Delhi, 110095, India

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Pune, 411 030, India

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Catanzaro, 88100, Italy

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Messina, 98122, Italy

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Milan, 20132, Italy

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Monza (MI), 20052, Italy

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Orbassano, 10043, Italy

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Pavia, 27100, Italy

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Rome, 00133, Italy

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Siena, 53100, Italy

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Turin, 10126, Italy

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Udine, 33100, Italy

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Podgorica, 81000, Montenegro

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Gdansk, 80-803, Poland

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Gdansk, 80266, Poland

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Katowice, 40752, Poland

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Krakow, 31-530, Poland

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Lodz, 90-153, Poland

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Lodz, 93-513, Poland

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Lublin, 20-718, Poland

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Poznan, 60-355, Poland

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Sosnowiec, 41-200, Poland

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Szczecin, 71252, Poland

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Warsaw, 00-416, Poland

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Warsaw, 09-777, Poland

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Kaliningrad, 236000, Russia

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Kazan', 420012, Russia

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Madrid, 28038, Russia

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Moscow, 117049, Russia

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Moscow, 117995, Russia

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Moscow, 198103, Russia

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Saint Petersburg, 194017, Russia

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Saint Petersburg, 194044, Russia

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Saint Petersburg, 197376, Russia

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Yaroslavl, 160000, Russia

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Belgrade, 11000, Serbia

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Kragujevac, 34000, Serbia

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Kruševac, 37000, Serbia

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Niš, 18000, Serbia

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Novi Sad, 21000, Serbia

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Sombor, 25000, Serbia

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Subotica, 24000, Serbia

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Bratislava, 80000, Slovakia

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Bratislava, 826 06, Slovakia

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Bratislava, 833 05, Slovakia

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Brezno, 97701, Slovakia

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Košice, 4190, Slovakia

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NoveZamky, 940 34, Slovakia

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Spitalska 6, 94901, Slovakia

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Vranov nad Topľou, 093 27, Slovakia

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Žilina, 1207, Slovakia

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Bellair, 4001, South Africa

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Berea, 4001, South Africa

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Parktown, 2193, South Africa

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Pretoria, 0041, South Africa

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Richards Bay, 3900, South Africa

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Sandton, 2196, South Africa

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Tygerberg, 7505, South Africa

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Umhlanga, 4320, South Africa

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Anyang, 431-070, South Korea

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Seoul, 110-744, South Korea

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Seoul, 133-792, South Korea

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Seoul, 143-729, South Korea

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Wŏnju, 220-701, South Korea

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Alicante, 03010, Spain

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Barcelona, 08041, Spain

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Cruces (Vizcaya), 48903, Spain

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Madrid, 28040, Spain

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Madrid, 28047, Spain

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Málaga, 29010, Spain

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Oviedo, 33006, Spain

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Seville, 41009, Spain

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Seville, 41013, Spain

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Seville, 41014, Spain

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Zaragoza, 50009, Spain

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Gothenburg, 41345, Sweden

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Linköping, SE-58185, Sweden

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Lund, 22185, Sweden

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Basel, 4031, Switzerland

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Bern, 3010, Switzerland

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Sankt Gallen, 9007, Switzerland

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Changhua, 50006, Taiwan

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Kaohsiung City, 80099, Taiwan

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Taoyuan District, 33305, Taiwan

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Yongkang District, 71004, Taiwan

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Bristol, BS16 1LE, United Kingdom

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Cardiff, CF144XN, United Kingdom

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Glasgow, G11 6NT, United Kingdom

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Liverpool, L9 7AJ, United Kingdom

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Tooting, SW17 0QT, United Kingdom

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Treliske, TR1 3LJ, United Kingdom

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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

• Michel Baulac

  Hopital de la Pitie-Saltpetriere

  PRINCIPAL INVESTIGATOR

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: February 19, 2009
• First Posted: February 20, 2009
• Study Start: October 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 24, 2015
• Results First Posted: January 15, 2013

Record last verified: 2015-11

Locations

DE (6); MO (1); PL (12); KR (5); TW (4); ZA (8); FR (4); GR (7); IT (10); HU (8); DK (1); CH (3); SE (7); SL (9); RU (10); ES (11); AU (8); GB (6); IN (10)