Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-blind Trial Comparing the Efficacy, Tolerability and Safety of Monotherapy Topiramate Versus Phenytoin in Subjects With Seizures Indicative of New Onset Epilepsy
Brief Summary: The purpose of this study is to compare the effectiveness and safety of two treatment regimens, topiramate as compared to phenytoin, in preventing seizures in patients with new-onset epilepsy who require rapid initiation of antiepileptic drug therapy. Reasons for requiring rapid initiation of treatment, rather than slowly increasing an antiepileptic drug to an effective dose, may include severe or frequent seizures, or high risk to the patient of recurrent seizures.


Options:
A: Inclusion Criteria:

* Seizures indicative of new-onset epilepsy (or epilepsy relapse) of untreated epilepsy
* at least one but not more than 20 unprovoked seizures within past 3 months
* weighing more than 110 pounds
* considered to be a good candidate for rapid initiation of anti-seizure medication
* able to swallow a tablet whole (without crushing it).

Exclusion Criteria:

* Not having taken anti-seizure medications within the past 30 days
* no provoking factors for seizures (presence of alcohol withdrawal, drug intoxication, acute meningitis or encephalitis, acute head injury or stroke, acute hypoxic/ischemic encephalopathy, or brain tumor)
* no presence of active liver disease or serious kidney disease
* not pregnant or breast-feeding
* not using birth control.
B: 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.
C: Inclusion Criteria:

* Age ≥ 12 years
* Body weight ≥ 30kg (patients 12-15 years of age) and ≥ 40kg (patients over 16 years of age), respectively
* Either one epileptic seizure with high risk of relapse (partial seizure semiology, MRI lesion or pathological focal EEG findings) or a newly diagnosed epilepsy (≥ 2 unprovoked seizures) with at least 1 seizure within the past 3 months before begin of trial participance
* Treatment with no or a maximum of one anticonvulsant drug at the time of inclusion
* Fertile women of ≥ 16 years of age must use at least one of the following contraceptives for at least one month prior to initiation of trial participance: Oral contraceptive, contraceptive diaphragm, intrauterine contraceptive device (coil), tube ligation. For girls between 12 and 15 years of age a written confirmation of sexual abstinence, given by a person having the care and custody of the child, is sufficient.
* Informed consent by the proband in written form after being informed about character, relevance and consequences of the clinical trial, and additional informed consent given by a person having the care and custody of the child for patients between 12 and 17 years of age, respectively.

Exclusion Criteria:

* Patients with non-epileptic seizures or acute symptomatic seizures whose cause can be corrected
* Patients who suffer from absence seizures or simple partial seizures without motor signs (aura) only
* Patients who had a chronic focal epilepsy or an epileptic state in their medical history
* Patients with progressive neurological, degenerative or malignant diseases which are clinically relevant from the investigator's point of view (e.g. cardiovascular or endocrinic diseases)
* Patients who have been treated with Levetiracetam or Lamotrigine before
* Patients with known manifest renal insufficiency (creatinine clearance \< 80 mL/min)
* Patients with known hypersensitivity to Levetiracetam, Lamotrigine or another component of the trial drugs
* Patients who are attended by a legal guardian
* Patients suffering from a psychiatric disease or affective disorders (within the past 6 months), which had to be treated with electric convulsive therapy, tranquilizing agents, monoamine oxidase inhibitors or CNS-active sympathomimetics (e.g. methylphenidate)
* Patients who were suffering from alcohol- or drug-addiction within the past 12 months
* Pregnant or breast-feeding women
* Patients who participated in another clinical trial within the past 30 days
D: For inclusion in the study, subjects must fulfill all of the following at the time points indicated:

Visit 1 (Days -1 to -7; Screening)

* Have signed an informed consent before undergoing any study-related activities. Subjects of Asian ancestry (subjects with a direct ancestor of Asian origin, irrespective of the generational difference) are required to give written informed consent for genotyping.
* Male or female ≥18 years of age.
* Newly diagnosed epilepsy with at least 2 well documented, unprovoked, clinically evaluated and classified partial seizures (with or without secondary generalization) with clear focal origin, documented clinically OR by electroencephalogram (EEG) OR by imaging studies, within 12 months of Visit 1. In this context, seizures that occur within a period of 48 hours are counted as one seizure.
* At least 1 seizure during the previous 3 months.
* Demonstrated cooperation and willingness to complete all aspects of the study.
* Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum ß-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study visit (PSV).

Visit A1 (Day 1; Randomization and start of double-blind treatment period)

* Have satisfactorily completed the electronic subject diary (eDiary).
* Female subjects with childbearing potential must not be pregnant as confirmed by a negative urine pregnancy test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the PSV.

Subjects having any of the following at the time points indicated are to be excluded from the study:

Visit 1 (Days -1 to -7)

* History of pseudo-seizures
* Seizures occurring only in clusters.
* History of absence, myoclonic, clonic, tonic, or atonic seizures.
* Documented EEG within 12 months of Visit 1 suggestive of primarily generalized epilepsy.
* History of status epilepticus within the 3 months prior to Visit 1.
* Known progressive neurologic disorder (progressive brain disease, epilepsy secondary to progressive cerebral lesion) as assessed by magnetic resonance imaging or computer tomography.
* Former or current use of any anti-epileptic drug (AED), except for the use of a single AED for a maximum duration of 2 weeks before Visit 1.
* Previous use of ESL or carbamazepine (CBZ).
* Using mono-amine oxidase inhibitors (MAOIs), tricyclic antidepressants, nefazodone, isoniazid, or protease inhibitors or any other anti-retroviral agents (e.g. efavirez) that may raise the levels of CBZ-CR.
* Known hypersensitivity to carboxamide derivatives or tricyclic antidepressants.
* History of uncontrolled psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months, a history of suicide attempt, schizophrenia, chronic treatment with benzodiazepines (except short-acting benzodiazepines) or barbiturates.
* Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (C-SSRS).
* History of alcohol, drug, or medication abuse within the last 2 years.
* Uncontrolled cardiac (including atrioventricular block and other clinically significant electrocardiographic abnormalities), renal, hepatic, endocrine, gastrointestinal, metabolic, hematological, or oncology disorder.
* History of bone marrow depression.
* History of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
* Relevant clinical laboratory abnormalities (e.g. sodium \<130 mmol/L, alanine or aspartate transaminases \>2 x the upper limit of normal, white blood cell count \<3000 cells/mm3) (measured at Visit 1).
* Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 (measured at Visit 1).
* Subjects of Asian ancestry who test positive for the presence of the HLA-B\*1502 allele.
* Pregnancy or lactating.
* Participation in other drug clinical trial within the last 2 months or having received an investigational medicinal product (IMP) within 5 half-lives of that IMP, whichever is longer.
* Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject's ability to comply with the study protocol.

Visit A1 (Day 1)

* Former or current use of any AED, except for the use of a single AED for a maximum duration of 2 weeks before Visit 1 and with a drug-free period of at least 5 days before Visit A1. Benzodiazepines are allowed, no more than twice a week, for an epileptic indication and as rescue medication during the ≥5-day drug-free period.
* Using prohibited medication.
* Pregnancy.
* Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject's ability to comply with the study protocol.

Answer: A