Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: Inclusion Criteria:

* Male or female subjects from 16 to 80 years, inclusive. Vulnerable subjects (e.g., under 20 years or subject with learning disability but judged to be capable to understand) may only be included where legally permitted and ethically accepted
* Subjects with newly or recently diagnosed epilepsy having experienced unprovoked partial seizures (IA, IB, IC with clear focal origin), that are classifiable according to the International Classification of Epileptic seizure (1981). Undiscriminated subjects between IC and IIE could be included
* Subjects with at least 2 unprovoked seizures separated by a minimum of 48 hours in the year preceding randomization out of which at least 1 unprovoked seizure in the 6 months preceding randomization
* Subjects with documented evidence of EEG and brain MRI or CT scan in medical records which were performed within 1 year prior to Visit 1 (V1)
* Subjects have no treatment with anti-epileptic drugs in the 6 months preceding this study. The treatment for acute seizure control is acceptable with a maximum of 2 weeks duration and if the treatment was stopped at least 1 week before V1. For Phenobarbital and Phenobarbital derivatives, a minimum of 4 weeks wash-out is requested before V1

Exclusion Criteria:

* Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events which could be confused with seizures
* Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: neuroleptics, monoamine oxidase (MAO) inhibitors and narcotic analgesics
* Subject taking any immunosuppressant within 28 days prior to Visit 1
* Subject has a history of suicide attempt, has received professional counseling for suicidal ideation, or is currently experiencing active suicidal ideation
* Subject has a seizure disorder characterized primarily by isolated auras (ie, simple partial seizures without observable motor signs)
* Subject suffering from seizures other than partial (IA, IB, IC, with clear focal origin) seizures
* Subject has a history of status epilepticus within last 3-month period prior to Visit 1
* Subject has seizures that are uncountable due to clustering (ie, an episode lasting less than 30 minutes in which several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) during the 12-week period prior to Visit 1 and/or during the Screening Period
* Body weight is lower than 40 kg (\< 40 kg)
B: Inclusion Criteria:

1. Patients from age 4 to 16, who have been diagnosed with focal epilepsy
2. Patients who have experienced minimal two unprovoked seizures, or patients who have had one unprovoked seizure and have shown focal abnormality in the EEG
3. Patients who have not received any antiepileptic medications prior to the study (Those who have been treated with rescue medication are eligible)
4. Patients with eligible consent or with legal guardians have given official consent

Exclusion Criteria:

1. Patients with progressive CNS disease, or systemic illness
2. Patients with level of SGOT/SPGT above the doubled normal level or BUN/Creatinine above the 3 times of the normal range
3. Patients who had used other anti-epileptic medication during any period of the trial, including baseline period. (Benzodiazepine used as rescue therapy is acceptable)
4. Patients who show hypersensitive reaction to the study medication.
5. Patients with any psychological problems.
6. Patients deemed inappropriate for the study by the investigators
C: 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 Ã¬mol / 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.
D: Inclusion criteria:

* Male or Female ≥13 years of age
* Have a confident diagnosis of epilepsy with partial seizures for at least 24 weeks prior to the Baseline Phase
* Have a documented history of partial seizures such that the investigator must judge that the subject is likely to have at least 4 partial seizures during the 8-week Baseline Phase.
* Have experienced at least 4 partial seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4-week (i.e., 28-day) period.
* NOTE: With prior authorization from GlaxoSmithKline (GSK), retrospective data may take the place of up to the first 4 weeks (i.e., first 28 days) of the Baseline Phase for subjects providing reliable documentation of the following:

  1. A complete daily seizure diary that includes the number, and type (i.e., simple or complex partial seizures with or without secondary generalization), of seizures experienced each day for up to 28 consecutive days immediately prior to the prospective Baseline Phase
  2. Stability of prescribed dosages of background antiepileptic drug (AED)
  3. Compliance with background AED

All subjects permitted to use retrospective baseline data must complete a minimum of four weeks (i.e., 28 days) of the prospective Baseline Phase. The retrospective plus the prospective Baseline Phases must equal the 56 consecutive days prior to the start of dosing with study drug.

* be currently receiving AED monotherapy treatment with a stable regimen of a non-enzyme inducing AED for at least four weeks prior to starting the Baseline Phase.
* be able and willing to maintain an accurate, complete, written daily seizure diary, or has a parent/caregiver who is able and willing to maintain and accurate, complete, written daily seizure diary for the entire duration of the study.
* be able to comply with the dosing of study drugs, background AED, and all study procedures.
* understand and sign written informed consent, or will have a parent or a legally authorized representative who has done so, prior to the performance of any study assessments
* if female, and of childbearing potential be using an acceptable form of birth control, to include one of the following:

  1. Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (a minimum of 2 weeks).
  2. Consistent and correct use of one of the following methods of birth control:

Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.

Any intrauterine device (IUD) with a documented failure rate of less than 1% per year

Double barrier method consisting of spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm).

NOTE: Women who have had a hysterectomy, tubal ligation, or are post-menopausal are considered to be of non-childbearing potential.

NOTE: A pharmacokinetic interaction has been observed between lamotrigine (LTG) and estrogen-based oral contraceptives. Therefore, the use of hormonal therapy (e.g., for contraception or hormone replacement therapy) is not allowed.

Exclusion criteria:

* Exhibits any primary generalized seizures (e.g., absence, myoclonic primary generalized tonic-clonic seizures).
* Has had status epilepticus within the 24 weeks prior to, or during, the Baseline Phase.
* Is taking an enzyme-inducing AED (EIAED - e.g. carbamazepine, phenytoin, phenobarbital, primidone) or is taking more than 1 background AED.
* Is currently taking lamotrigine (LTG) or has previously had an adequate trial of LTG.
* Is currently taking felbamate
* Is using hormone therapy
* Is abusing alcohol and/or other substances
* Has taken an investigational drug within the previous 30 days or plans to take an investigational drug anytime during the study.
* Is receiving chronic treatment with any medication that could influence seizure control
* NOTE: Use of benzodiazepines is allowed as specified in Section 8.1.2
* Is currently following the ketogenic diet.
* Is using vagal nerve stimulation
* Is planning surgery to control seizures during the study.
* Is pregnant, breastfeeding, or planning to become pregnant during the study or within the three weeks after the last dose of study drug.
* Is suffering from acute or progressive neurological disease, severe psychiatric disease or severe mental abnormality that is likely to interfere with the objectives of the study.
* Has any clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.

Answer: C