Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy - Full Text View

Sponsor:	Philipps University Marburg Medical Center
Collaborator:	UCB GmbH, Hüttenstrasse 205, 50170 Kerpen-Sindorf, Germany
Information provided by:	Philipps University Marburg Medical Center
ClinicalTrials.gov Identifier:	NCT00242606

Purpose

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.

Condition	Intervention	Phase
Epilepsy	Drug: Lamotrigine Drug: Levetiracetam	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy: An Open, Prospective, Multicenter, Randomized Phase III Study

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Lamotrigine Levetiracetam

U.S. FDA Resources

Further study details as provided by Philipps University Marburg Medical Center:

Primary Outcome Measures:

Rate of seizure-free patients [ Time Frame: in the first 6 weeks of the trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of seizure-free patients [ Time Frame: during the last 16 weeks ] [ Designated as safety issue: No ]
rate of seizure-free patients [ Time Frame: during the total 26 weeks of the observation period ] [ Designated as safety issue: No ]
time until the first seizure appears [ Time Frame: untin week 26 ] [ Designated as safety issue: No ]
time patients take the study medication [ Time Frame: until week 26 ] [ Designated as safety issue: No ]
safety [ Time Frame: until end of week 26 ] [ Designated as safety issue: Yes ]
quality of life during treatment [ Time Frame: until week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment:	410
Study Start Date:	March 2005
Estimated Study Completion Date:	August 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Levetiracetam 2000mg/day	Drug: Levetiracetam titrate to 2000mg/day over 22 days, maintain until the end of week 26
2: Active Comparator Lamotrigine	Drug: Lamotrigine titrate to 200mg over 10 weeks and maintained until end of week 26

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

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00242606

Contacts

Contact: Felix Rosenow, M.D.	+4964212865348	rosenow@staff.uni-marburg.de
Contact: Sebastian Bauer, M.D.	+4964212865200	bauerse@med.uni-marburg.de

Locations

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

Sponsors and Collaborators

Philipps University Marburg Medical Center

UCB GmbH, Hüttenstrasse 205, 50170 Kerpen-Sindorf, Germany

Investigators

Principal Investigator:

Felix Rosenow, M.D.

Philipps University Marburg Medical Center

More Information

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.

Responsible Party:	Universitätsklinikum Giessen und Marburg GmbH ( Prof. Dr. Felix Rosenow )
Study ID Numbers:	LaLiMo
Study First Received:	October 19, 2005
Last Updated:	May 20, 2008
ClinicalTrials.gov Identifier:	NCT00242606 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Philipps University Marburg Medical Center:

Newly diagnosed epilepsy
Initial monotherapy
Levetiracetam
Lamotrigine

Additional relevant MeSH terms:

Nootropic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nervous System Diseases
Central Nervous System Diseases
Calcium Channel Blockers
Cardiovascular Agents
Brain Diseases
Protective Agents
Neuroprotective Agents

Pharmacologic Actions
Membrane Transport Modulators
Epilepsy
Therapeutic Uses
Lamotrigine
Piracetam
Etiracetam
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on November 27, 2009