Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy

Condition(s) targeted: Epilepsy

Intervention: Lamotrigine (Drug); Levetiracetam (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Philipps University Marburg Medical Center

Official(s) and/or principal investigator(s):
Felix Rosenow, M.D., Principal Investigator, Affiliation: Philipps University Marburg Medical Center

Overall contact:
Felix Rosenow, M.D., Phone: +4964212865348, Email: rosenow@staff.uni-marburg.de

The purpose of this study is to compare the efficacy, safety and tolerance of the drugs Lamotrigine and Levetiracetam in the initial monotherapy of patients with newly diagnosed epilepsy.

Official title: Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy: An Open, Prospective, Multicenter, Randomized Phase III Study

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Rate of seizure-free patients

Secondary outcome:

Rate of seizure-free patients

rate of seizure-free patients

time until the first seizure appears

time patients take the study medication

safety

quality of life during treatment

Detailed description:

Epilepsy is the second most frequent neurologic disease (prevalence 0. 5 % - 1 % [Brodie et

al. 1997]). About 30 % of epilepsy patients (including many children) suffer from intractable seizures [Kwan & Brodie 2000]. Therefore new drugs and an expansion of permission for drugs with limited approval, respectively, are needed.

Levetiracetam is a new potent antiepileptic drug with nearly ideal pharmacokinetic properties and few side effects [Patsalos 2000], but it is approved in Germany only for add-on therapy for patients > 15 years of age with focal epilepsy.

Due to its few cognitive side effects and its efficacy, Lamotrigine is becoming standard therapy for focal and generalized epilepsy for patients from >11 years of age. Its disadvantage is the possibility of severe allergic reactions which limits the speed of dose increment.

Comparisons: Patients with newly diagnosed epilepsy are treated with either Lamotrigine or Levetiracetam. Rate of seizure-free patients in the first 6 weeks of the trial (main outcome criterion) as well as rate of seizure-free patients during the last 16 weeks and the total 26 weeks of the observation period, time until the first seizure appears, time patients take the study medication, safety and quality of life during treatment are compared.

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Felix Rosenow, M.D., Phone: +4964212865348, Email: rosenow@staff.uni-marburg.de

Philipps University Marburg Medical Center, Department of Neurology, Marburg 35033, Germany; Recruiting
Felix Rosenow, M.D., Phone: +4964212865348, Email: rosenow@staff.uni-marburg.de
Sebastian Bauer, M.D., Phone: +4964212865200, Email: bauerse@med.uni-marburg.de
Felix Rosenow, M.D., Principal Investigator
Karl-Martin Klein, M.D., Sub-Investigator

Related publications:

Brodie MJ, Shorvon SD, Canger R, Halasz P, Johannessen S, Thompson P, Wieser HG, Wolf P. Commission on European Affairs: appropriate standards of epilepsy care across Europe.ILEA. Epilepsia. 1997 Nov;38(11):1245-50. No abstract available.

Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000 Feb;85(2):77-85. Review.

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9.

Starting date: March 2005
Ending date: August 2008
Last updated: May 20, 2008