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Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy

Primary Purpose

Epilepsy

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Lamotrigine
Levetiracetam
Sponsored by
Philipps University Marburg Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Newly diagnosed epilepsy, Initial monotherapy, Levetiracetam, Lamotrigine

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Philipps University Marburg Medical Center, Department of Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Levetiracetam 2000mg/day

Lamotrigine

Outcomes

Primary Outcome Measures

Rate of seizure-free patients

Secondary Outcome Measures

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

Full Information

First Posted
October 19, 2005
Last Updated
May 8, 2012
Sponsor
Philipps University Marburg Medical Center
Collaborators
UCB Pharma GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT00242606
Brief Title
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

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Philipps University Marburg Medical Center
Collaborators
UCB Pharma GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Newly diagnosed epilepsy, Initial monotherapy, Levetiracetam, Lamotrigine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
409 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Levetiracetam 2000mg/day
Arm Title
2
Arm Type
Active Comparator
Arm Description
Lamotrigine
Intervention Type
Drug
Intervention Name(s)
Lamotrigine
Intervention Description
titrate to 200mg over 10 weeks and maintained until end of week 26
Intervention Type
Drug
Intervention Name(s)
Levetiracetam
Intervention Description
titrate to 2000mg/day over 22 days, maintain until the end of week 26
Primary Outcome Measure Information:
Title
Rate of seizure-free patients
Time Frame
in the first 6 weeks of the trial
Secondary Outcome Measure Information:
Title
Rate of seizure-free patients
Time Frame
during the last 16 weeks
Title
rate of seizure-free patients
Time Frame
during the total 26 weeks of the observation period
Title
time until the first seizure appears
Time Frame
untin week 26
Title
time patients take the study medication
Time Frame
until week 26
Title
safety
Time Frame
until end of week 26
Title
quality of life during treatment
Time Frame
until week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felix Rosenow, M.D.
Organizational Affiliation
Philipps University Marburg Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Philipps University Marburg Medical Center, Department of Neurology
City
Marburg
ZIP/Postal Code
35033
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
9579928
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.
Results Reference
background
PubMed Identifier
10722121
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.
Results Reference
background
PubMed Identifier
10660394
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.
Results Reference
background
PubMed Identifier
22595362
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.
Results Reference
derived

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Lamotrigine Versus Levetiracetam in the Initial Monotherapy of Epilepsy

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