Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs - Full Text View

Sponsor:	Johannes Gutenberg University Mainz
Information provided by (Responsible Party):	Konrad J. Werhahn, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier:	NCT00438451

Purpose

In this clinical trial patients with newly diagnosed focal epilepsy aged 60 years or older receive three different antiepileptic drugs in a double-blind, randomized design over a period of 58 weeks. All drugs are licensed for the treatment of epilepsy. The primary endpoint of this study will be retention rate at 58-weeks, since it reflects both efficacy and tolerability.

Condition	Intervention	Phase
Focal Epilepsy	Drug: Levetiracetam Drug: carbamazepine slow release Drug: lamotrigine	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicentre, Double-blind, Randomized, Phase IV Clinical Trial Comparing the Safety, Tolerability and Efficacy of Levetiracetam Versus Lamotrigine and Carbamazepine in the Oral Antiepileptic Therapy of Newly Diagnosed Elderly Patients With Focal Epilepsy.

Resource links provided by NLM:

Genetics Home Reference related topics: autosomal dominant partial epilepsy with auditory features pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Lamotrigine Levetiracetam Carbamazepine

U.S. FDA Resources

Further study details as provided by Johannes Gutenberg University Mainz:

Primary Outcome Measures:

58-week retention rate measured by the number of drop outs due to adverse events or seizures from day 1 of treatment [ Time Frame: 58 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients remaining seizure-free at week 30 (Visit 4) [ Time Frame: week 30 ] [ Designated as safety issue: No ]
Proportion of patients remaining seizure free at week 58 (Visit 6) [ Time Frame: week 58 ] [ Designated as safety issue: No ]
The time (in days) to first break-through seizure (from day 1 of treatment) [ Time Frame: over the whole duration of 58 weeks ] [ Designated as safety issue: No ]
The absolute seizure frequency during the maintenance (over 52 weeks) phase [ Time Frame: over 52 weeks ] [ Designated as safety issue: Yes ]
Proportion of seizure-free days during the maintenance phase for subjects who enter the maintenance phase [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
The frequency of adverse events (from day 1 of treatment) [ Time Frame: 58 weeks ] [ Designated as safety issue: Yes ]
QOLIE-31 results at V6 [ Time Frame: 58 weeks, final visit ] [ Designated as safety issue: No ]
Portland Neurotoxicity scale at V6 [ Time Frame: at week 58 ] [ Designated as safety issue: No ]
Results of cognitive testing (EpiTrack© by UCB) [ Time Frame: before, after 6 months and 58 weeks ] [ Designated as safety issue: No ]

Enrollment:	361
Study Start Date:	January 2007
Study Completion Date:	August 2011
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Levetiracetam	Drug: Levetiracetam LEV 250 mg capusles: week 1 and 2 0-0-1, week 3 and 4 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 per day (500 - 3000 mg)during maintenance.
Active Comparator: Carabamazepine SR	Drug: carbamazepine slow release CBZ 100 mg capusles: week 1 and 2: 0-0-1, week 3 and 4: 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 per day (200 - 1200 mg) during maintenance depending on tolerance and efficacy.
Active Comparator: Lamotrigine	Drug: lamotrigine LTG 25 mg encapsulated: week 1 and 2: 0-0-1, week 3 and 4: 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 caps. per day (50 - 300 mg)during maintenance depending on tolerance and efficacy.

Detailed Description:

Indication: Focal Epilepsy Objectives: To evaluate the tolerability and efficacy of levetiracetam (LEV) in newly diagnosed elderly patients (aged 60 yrs or above) with focal epilepsy compared to lamotrigine (LTG) or carbamazepine slow release (CBZ).

Primary Outcome: The primary outcome will be the 58-week retention rate measured by the number of drop outs due to adverse events or seizures from day 1 of treatment.

Secondary Outcome: Proportion of patients remaining seizure-free at week 30 (Visit 4); proportion of patients remaining seizure free at week 58 (Visit 6); the time (in days) to first break-through seizure (from day 1 of treatment); the absolute seizure frequency during the maintenance (over 52 weeks) phase; proportion of seizure-free days during the maintenance phase for subjects who enter the maintenance phase; the frequency of adverse events (from day 1 of treatment); QOLIE-31 results at V6; Portland Neurotoxicity scale at V6; results of cognitive testing (EpiTrack© by UCB).

Trial Design: This is a randomized, double-blind, multicenter Phase IV study using a parallel group design with three treatment groups. The study will consist of a 6-week titration-phase and a 52-week maintenance phase. Patients who successfully complete the trial (final visit, V6) will be unblinded and offered either to continue on their current drug or be changed to an alternative antiepileptic drug (AED) treatment of choice.

Population: Patients aged 60 years or above with new onset focal epilepsy i.e. either at least one epileptic seizure in the last 6 months and focal epileptiform discharges on EEG or a relevant lesion on CT/MRI or a total of 2 epileptic seizures, one of which occurring in the last 6 months prior inclusion. Patients with acute (< 2 weeks) symptomatic epileptic seizures due to acute brain abnormalities (i.e. haemorrhage or cerebral infarct), or contraindications against any of the drugs in trial will be excluded.

Sample Size: 360 patients to be included, 120 patients per treatment arm. Investigational Medicinal Product(s): Levetiracetam, lamotrigine, carbamazepine-slow release Trial Duration and Dates: Duration of treatment: 6 weeks titration phase, 52 weeks maintenance phase.

Follow up: At the end of trial subjects will be unblinded and may choose to continue on the medication or taper the trial medication and be treated with an alternative drug at the investigators discretion. The patient will receive a dosing schedule and a referral letter for his/her physician.

Duration of trial: approximately 2 years. Start of recruitment: January 2007 Projected number of centres: 75 Number of countries: 3 (Germany, Switzerland, Austria).

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 60 yrs or above.
New onset focal epilepsy i.e. either at least one epileptic seizure in the last 6 months and focal epileptiform discharges on EEG or a relevant lesion on CT/MRI or at least 2 epileptic seizures, one of which occurring in the last 6 months prior inclusion.
No previous AED treatment, except for a period not longer than 4 weeks prior to inclusion (V0).
Ability of subject to understand verbal and written instructions, to comply with all study requirements, and to comprehend character and individual consequences of the clinical trial.
Written informed consent before enrolment in the trial.

Exclusion Criteria:

Acute symptomatic epileptic seizures occurring acutely within a 2 week period after the onset of an acute illness such as cerebral haemorrhage, cerebral infarct, rapid progressive malignancy or other acute brain abnormalities (i.e. encephalitis, hypoxic brain damage, trauma, metabolic derangement, following brain surgery).
Dementia (as defined by history)
Renal insufficiency as defined by GFR < 50 mL/min.
Increased liver enzymes (GOT, GPT, gGT) or increased bilirubin ≥ 2-fold the upper limit of normal (ULN).
Pre-treatment with valproic acid within the four weeks prior inclusion (V0).
Contraindication against or history of hypersensitivity to any of the investigational medicinal products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal products.
Participation in other clinical trials and observation period of competing trials within the last 2 months, respectively.
History of drug or alcohol abuse within the last 2 years.
Medical condition which interferes with the participation in the trial according to the opinion of the investigator.
Patients with life expectancy < 1 year due to malignant disease
Psychiatric morbidity requiring legal guardianship.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438451

Locations

Germany
Department of Neurology, University of Mainz Medical Centre
Mainz, Germany, 55101

Sponsors and Collaborators

Johannes Gutenberg University Mainz

Investigators

Study Chair:	Konrad J Werhahn, MD	Johannes Gutenberg University, Department od Neurology
Study Director:	Günter Kraemer, MD	Swiss Epilepy Centre
Study Director:	Eugen Trinka, MD	Medical University of Salzburg, Department of Neurology, Austria

More Information

Publications:

Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML; VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(11):1868-73.

Brodie MJ, Chadwick DW, Anhut H, Otte A, Messmer SL, Maton S, Sauermann W, Murray G, Garofalo EA; Gabapentin Study Group 945-212. Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy. Epilepsia. 2002 Sep;43(9):993-1000.

Responsible Party:	Konrad J. Werhahn, Prof of Neurology, Head Section on Epilepsy, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier:	NCT00438451 History of Changes
Other Study ID Numbers:	STEPONE05, ISRCTN: 94839639, EudraCT Number:2005-003324-19
Study First Received:	February 21, 2007
Last Updated:	December 2, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; Austria: Agency for Health and Food Safety; Switzerland: Swissmedic

Keywords provided by Johannes Gutenberg University Mainz:

elderly
focal epilepsy
anticonvulsive
treatment

levetiracetam
lamotrigine
carbamazepine

Additional relevant MeSH terms:

Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Etiracetam
Anticonvulsants
Carbamazepine
Piracetam
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Nootropic Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on February 12, 2012