Clinical trial NCT00242606: Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy
Official title: Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy: An Open, Prospective, Multicenter, Randomized Phase III Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Newly diagnosed epilepsy
Initial monotherapy
Levetiracetam
Lamotrigine
Lead sponsor: Philipps University Marburg
Sponsor class: OTHER
Collaborators: name: UCB Pharma GmbH
First posted: 2005-10-20
Enrollment: 409
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Rate of seizure-free patients
timeFrame: in the first 6 weeks of the trial
Secondary outcomes:
measure: Rate of seizure-free patients
timeFrame: during the last 16 weeks
measure: rate of seizure-free patients
timeFrame: during the total 26 weeks of the observation period
measure: time until the first seizure appears
timeFrame: untin week 26
measure: time patients take the study medication
timeFrame: until week 26
measure: safety
timeFrame: until end of week 26
measure: quality of life during treatment
timeFrame: until week 26
Other outcomes:
Locations:
city: Marburg
country: Germany
facility: Philipps University Marburg Medical Center, Department of Neurology
Study officials:
affiliation: Philipps University Marburg
name: Felix Rosenow, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1111/j.1528-1157.1997.tb01224.x. No abstract available.
citation: Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000 Feb;85(2):77-85. doi: 10.1016/s0163-7258(99)00052-2.
citation: Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.
citation: Rosenow F, Schade-Brittinger C, Burchardi N, Bauer S, Klein KM, Weber Y, Lerche H, Evers S, Kovac S, Hallmeyer-Elgner S, Winkler G, Springub J, Niedhammer M, Roth E, Eisensehr I, Berrouschot J, Arnold S, Schroder M, Beige A, Oertel WH, Strzelczyk A, Haag A, Reif PS, Hamer HM; LaLiMo Study Group. The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy--an open-label, prospective, randomised controlled multicenter study. J Neurol Neurosurg Psychiatry. 2012 Nov;83(11):1093-8. doi: 10.1136/jnnp-2011-301999. Epub 2012 May 17.