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

A Randomized, Double-Blind Extension Study To Assess The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Zonisamide; Drug: Carbamazepine

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland, Australia, 4558
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
  • Victoria
    • Clayton, Victoria, Australia, 3168
    • Fitzroy, Victoria, Australia, 3065
    • Heidelberg West, Victoria, Australia, 3084
    • Parkville, Victoria, Australia, 3050
  • Western Australia
    • Perth, Western Australia, Australia, 6000
• Denmark
  • Aalborg, Denmark, 9000
• France
  • Bethune cedex, France, 62408
  • Dijon cedex, France, 21033
  • Paris, France, 75651
  • St Etienne cedex 2, France, 42055
• Germany
  • Berlin, Germany, 13353
  • Bochum, Germany, 44805
  • Duesseldorf, Germany, 40212
  • Munich, Germany, 81377
  • Schwerin, Germany, 19053
  • Westerstede, Germany, 26676
• Greece
  • Athens, Greece, 11525
  • Athens, Greece, 10676
  • Athens, Greece, 15562
  • Patras, Greece, 26500
  • Thessaloniki, Greece, 54636
  • Thessaloniki, Greece, 57010
  • Thessaloniki, Greece, 55236
• Hungary
  • Budapest, Hungary, 1145
  • Budapest, Hungary, 1076
  • Budapest, Hungary, 1096
  • Debrecen, Hungary, 4032
  • Gyula, Hungary, 5700
  • Hodmezovasarhely, Hungary, 6800
  • Nyregyhaza, Hungary, 4400
  • Zalaegerszeg-Poozva, Hungary, 8908
• India
  • Bangalore, India, 560034
  • Bangalore, India, 560094
  • Hyderabad, India, 500 001
  • Koturpuram, Chennai, India, 600 085
  • Madurai, Tamil Nadu, India, 625 020
  • Mumbai, India, 400 012
  • New - Delhi, India, 110095
  • New Delhi, India, 110 016
  • New Delhi, India, 110 065
  • Pune, India, 411 030
• Italy
  • Catanzaro, Italy, 88100
  • Messina, Italy, 98122
  • Milan, Italy, 20132
  • Monza (MI), Italy, 20052
  • Orbassano, Italy, 10043
  • Pavia, Italy, 27100
  • Rome, Italy, 00133
  • Siena, Italy, 53100
  • Turin, Italy, 10126
  • Udine, Italy, 33100
• Korea, Republic of
  • Anyang, Korea, Republic of, 431-070
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 143-729
  • Seoul, Korea, Republic of, 133-792
  • Wonju, Korea, Republic of, 220-701
• Montenegro
  • Podgorica, Montenegro, 81000
• Poland
  • Gdansk, Poland, 80-803
  • Gdansk, Poland, 80266
  • Katowice, Poland, 40752
  • Krakow, Poland, 31-530
  • Lodz, Poland, 90-153
  • Lodz, Poland, 93-513
  • Lublin, Poland, 20-718
  • Poznan, Poland, 60-355
  • Sosnowiec, Poland, 41-200
  • Szczecin, Poland, 71252
  • Warszawa, Poland, 00-416
  • Warszawa, Poland, 09-777
• Russian Federation
  • Kaliningrad, Russian Federation, 236000
  • Kazan, Russian Federation, 420012
  • Madrid, Russian Federation, 28038
  • Moscow, Russian Federation, 117049
  • Moscow, Russian Federation, 117995
  • Moscow, Russian Federation, 198103
  • Saint Petersburg, Russian Federation, 194044
  • Saint-Petersburg, Russian Federation, 194017
  • Saint-Petersburg, Russian Federation, 197376
  • Yaroslavl, Russian Federation, 160000
• Serbia
  • Belgrade, Serbia, 11000
  • Kragujevac, Serbia, 34000
  • Krusevac, Serbia, 37000
  • Nis, Serbia, 18000
  • Novi Sad, Serbia, 21000
  • Sombor, Serbia, 25000
  • Subotica, Serbia, 24000
• Slovakia
  • Bratislava, Slovakia, 826 06
  • Bratislava, Slovakia, 833 05
  • Bratislava, Slovakia, 80000
  • Brezno, Slovakia, 97701
  • Kosice, Slovakia, 4190
  • NoveZamky, Slovakia, 940 34
  • Spitalska 6, Slovakia, 94901
  • Vranov nad Toplou, Slovakia, 093 27
  • Zilina, Slovakia, 1207
• South Africa
  • Bellair, South Africa, 4001
  • Berea, South Africa, 4001
  • Parktown, South Africa, 2193
  • Pretoria, South Africa, 0041
  • Richards Bay, South Africa, 3900
  • Sandton, South Africa, 2196
  • Tygerberg, South Africa, 7505
  • Umhlanga, South Africa, 4320
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08041
  • Cruces (Vizcaya), Spain, 48903
  • Madrid, Spain, 28040
  • Madrid, Spain, 28047
  • Malaga, Spain, 29010
  • Oviedo, Spain, 33006
  • Sevilla, Spain, 41014
  • Sevilla, Spain, 41013
  • Sevilla, Spain, 41009
  • Zaragoza, Spain, 50009
• Sweden
  • Goteborg, Sweden, 41345
  • Linkoping, Sweden, SE-58185
  • Lund, Sweden, 22185
• Switzerland
  • Basel, Switzerland, 4031
  • Berne, Switzerland, 3010
  • St Gallen, Switzerland, 9007
• Taiwan
  • Changhua, Taiwan, 50006
  • Kaohsiung, Taiwan, 80099
  • Tao-Yuan, Taiwan, 33305
  • Yong Kang, Taiwan, 71004
• United Kingdom
  • Bristol, United Kingdom, BS16 1LE
  • Cardiff, United Kingdom, CF144XN
  • Glasgow, United Kingdom, G11 6NT
  • Liverpool, United Kingdom, L9 7AJ
  • Tooting, United Kingdom, SW17 0QT
  • Treliske, United Kingdom, TR1 3LJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has completed study E2090-E044-310.
2. Subject is able and willing to give written informed consent.
3. 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.
4. The subject is able and willing to follow the investigational study procedures, maintain a seizure diary and report adverse events.

Exclusion Criteria:

1. 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.
2. Subject has a body weight <40 kg.
3. 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).
4. 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.
5. Subject is currently taking carbonic anhydrase inhibitors.
6. Subject developed pancreatitis, nephrolithiasis or hypercalcuria, clinically significant laboratory abnormalities, stroke or uncontrolled hypertension during study E2090-E044-310.
7. Subject is currently taking monoamine oxidase inhibitors (MAOIs) or any other excluded medications (see protocol section 9.9.3).
8. Subject has a history of allergy to carbamazepine or to zonisamide or to any of their ingredients or to sulphonamides.
9. Subject has developed a bone marrow depression, low platelet count or other blood dyscrasias.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ZNS	Drug: Zonisamide; 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.; Other Names: Zonegran
Active Comparator: CBZ	Drug: Carbamazepine; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Drop-out Due to Lack of Efficacy	Lack of efficacy was if the subject had poor seizure control (defined as experiencing a seizure despite being on the maximum dose for = 2 weeks). The subject could withdraw at any time 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)	Adverse events in study subjects included any change in the subject's condition. This includes symptoms, physical findings, or clinical syndromes. All AEs that occurred after signing of informed consent through the last visit and for 15 days following study drug discontinuation were captured on the AE Case Report Form (CRF).	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	The number of participants that have remained seizure free for at least a 24 month consecutive period from the start of the Flexible Dosing Period (FDP: the period following the Titration Period and leading into the Maintenance Period) in the base study through the treatment period of this study. Seizure freedom was defined as the absence of all seizure regardless of seizure type.	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	The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry,emotional well being,energy/fatigue, cognitive functioning, medication effects, social functioning,overall QOL. The overall score is derived by weighing and then summing the 7 domain scores. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are converted to 0-100 point scores; higher converted scores always reflect better QOL.	Weeks 0, 26, 52, 78 and 117

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Principal Investigator: Michel Baulac, Hopital de la Pitie-Saltpetriere

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: February 19, 2009
• First Submitted That Met QC Criteria: February 19, 2009
• First Posted (Estimate): February 20, 2009

Study Record Updates

• Last Update Posted (Estimate): December 24, 2015
• Last Update Submitted That Met QC Criteria: December 21, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Epilepsy; Monotherapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Cytochrome P-450 CYP3A Inducers; Zonisamide; Carbamazepine
• Other Study ID Numbers: E2090-E044-314; 2008-001159-23 (EudraCT Number)