A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
Information source: Eisai Inc.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Epilepsy
Intervention: Zonisamide (Drug); Carbamazepine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Eisai Inc. Official(s) and/or principal investigator(s): Joanna Segieth, Study Director, Affiliation: Eisai Limited
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.
Clinical Details
Official title: A Randomized, Multi-centre, Double-blind Study, to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase
Secondary outcome: Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance PeriodAnalysis of Time to Drop Out Due to an Adverse Event (AE) Analysis of Time to Drop Out Due to Lack of Efficacy Time to 6-months Seizure Freedom Time to 12-months Seizure Freedom Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1 Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1 Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
INCLUSION CRITERIA:
Subjects will be eligible for the study if they meet all of the following inclusion
criteria:
1. Male or female subjects, 18 to 75 years of age inclusive.
2. 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).
3. 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).
4. Subjects have a documented electroencephalogram (EEG) within 12 months of the
Screening Visit, compatible with localization-related epilepsy (to exclude primary
generalized epilepsy).
5. 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.
6. 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.
7. Subjects who are able and willing to follow investigational study procedures,
maintain a seizure diary, and report AEs.
8. Subjects who are able and willing to give written informed consent.
EXCLUSION CRITERIA:
Subjects who meet any of the following exclusion criteria will not be eligible for the
study:
1. 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).
2. Subjects with a history of absence, myoclonic, clonic, tonic, or atonic seizures.
3. Subjects have a history of status epilepticus, and/or non-epileptic seizures (e. g.,
metabolic, pseudo-seizures).
4. Subjects have experienced seizures relating to drugs, alcohol, acute medical illness,
mental retardation, or subjects with situation-related seizures.
5. Subjects have progressive encephalopathy or findings consistent with progressive CNS
disease or lesion (e. g. infection, demyelination, or tumour).
6. 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.
7. Subjects have been previously treated with carbamazepine or zonisamide.
8. Subjects have received an investigational drug or device in the three months prior to
the Screening Visit.
9. Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, or
tricyclic antidepressants.
10. Subjects have a history of bone marrow depression, low platelet count or other blood
dyscrasia.
11. Subjects have a history of acute intermittent porphyria.
12. 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.
13. Subjects have a body weight of less than 40 kg.
14. 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).
15. 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.
16. Subjects are currently taking carbonic anhydrase inhibitors.
17. Subjects have a history of pancreatitis, nephrolithiasis or hypercalcuria, clinically
significant laboratory or electro-cardiographic abnormalities, or uncontrolled
hypertension.
18. Subjects are currently taking mono-amine oxidase inhibitors (MAOIs) or any other
excluded medications.
Locations and Contacts
Camperdown, Australia
Clayton, Australia
Fitzroy, Australia
Flinders, Australia
Heidelberg West, Australia
Parkville, Australia
Queensland, Australia
Wellington, Australia
Aalborg, Denmark
Bethune cedex, France
Dijon, France
Paris, France
St. Etienne, France
Berlin, Germany
Bochum, Germany
Duesseldorf, Germany
Munich, Germany
Schwerin, Germany
Westerstede, Germany
Athens, Greece
Thessaloniki, Greece
Budapest, Hungary
Debrecen, Hungary
Gyula, Hungary
Hodmezovasarhely, Hungary
Nyregyhaza, Hungary
Zalaegerszeg-Pozva, Hungary
Bangalore, India
Hyderabad, India
Koturpuram, India
Madurai, India
New Delhi, India
Pune, India
Milan, Italy
Monza, Italy
Orbassano, Italy
Rome, Italy
Anyang, Korea, Republic of
Seol, Korea, Republic of
Seoul, Korea, Republic of
Wonju, Korea, Republic of
Gdansk, Poland
Katowice, Poland
Krakow, Poland
Lodz, Poland
Lublin, Poland
Poznan, Poland
Sosnowiec, Poland
Szcecin, Poland
Warszawa, Poland
Kaliningrad, Russian Federation
Kazan, Russian Federation
Moscow, Russian Federation
Saint Petersburg, Russian Federation
Yaroslavl, Russian Federation
Belgrade, Serbia
Nis, Serbia
Novi Sad, Serbia
Subotica, Serbia
Bratislava, Slovakia
Bratslava, Slovakia
Brezno, Slovakia
Nove Zamky, Slovakia
Vranov nad Toplou, Slovakia
Zilina, Slovakia
Sandton, South Africa
Alicante, Spain
Bacelona, Spain
Barcelona, Spain
Madrid, Spain
Malaga, Spain
Oviedo, Spain
Sevilla, Spain
Goteborg, Sweden
Lund, Sweden
Changhua, Taiwan
Yong Kang, Taiwan
Bristol, United Kingdom
Liverpool, United Kingdom
Treliske, United Kingdom
Additional Information
Starting date: May 2007
Last updated: June 26, 2014
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