- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00438451
Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs (STEP-ONE)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Mainz, Germany, 55101
- Department of Neurology, University of Mainz Medical Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Levetiracetam
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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.
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Active Comparator: Carbamazepine
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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.
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Active Comparator: Lamotrigine
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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58 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Drop Out
Time Frame: 58 weeks
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number of days between randomization and premature discontinuation of the study
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58 weeks
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Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)
Time Frame: Week 30
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Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30.
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Week 30
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Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)
Time Frame: week 58
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Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58.
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week 58
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The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)
Time Frame: over the whole duration of 58 weeks
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over the whole duration of 58 weeks
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The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)
Time Frame: over 52 weeks
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Seizure frequency was assessed by investigators in the CRF at the Visits V3, V4, V5 and V6. The absolute seizure frequency during the maintenance phase was defined as the sum of those entries. |
over 52 weeks
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Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase
Time Frame: 52 weeks
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52 weeks
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QOLIE-31 (Quality Of Life In Epilepsy) Results at V6
Time Frame: 58 weeks, final visit
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The QOLIE-31 is a 31 item score that measures the quality of life in epilepsy (each item with a range of 0 to 100).
There are 7 sub-scores seizure worry (items 11,21,22,23,25), overall quality of life (items 1,14), emotional well-being (items 3,4,5,7,9), energy/fatigue (items 2,6,8,10), cognitive functioning (items 12,15,16,17,18,26), medication effects (items 24,29,30) and social functioning (13,19,20,27,28).
These scores were combined to a total score by Total score = seizure worry*0.08 + overall quality of life*0.14
+ emotional well-being*0.15
+ energy/fatigue*0.12
+ cognitive functioning*0.27
+ medication effects*0.03
+ social functioning*0.21
For all scores, higher values indicate better quality of life.
Each score has a possible range from 0 to 100.
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58 weeks, final visit
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Portland Neurotoxicity Scale (PNS) at V6
Time Frame: at week 58
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The PNS is a 15-item scale. Each item can be scored from 1 to 9. There are a total score (includes all items, range:15 to 135) and two subscores: The cognitive toxicity subscore (10 items: Energy Level, Memory, Interest, Concentration, Forgetfulness, Sleepliness, Moodiness, Alertness, Attention Span, Motivation, range:10 to 90) and the somatomoto subscore (5 items: Vision, Walking, Coordination, Tremor, Speech, range:5-45). The score is calculated by taking the mean of all non-missing values times the number of items. Lower values indicate better quality of life. |
at week 58
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Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6
Time Frame: week 58
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EPITrack-Score shows the performance of attention and executive functions.
Higher values indicate a better performance.
The results of EPITrack Score ranges between 7 and 45.
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week 58
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Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6
Time Frame: 58 weeks
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Evaluation of current testing at V6: ≥29 score points: Inconspicuous; 26 to 28 score points: Borderline; ≤25 score points: Impaired |
58 weeks
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Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6)
Time Frame: week 58
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Evaluation of Changes Changes in the EpiTrack® Score were categorized as follows: ≥5 score points: Improved; -3 to 4 score points: Unchanged; ≤-4 score points: Worsened |
week 58
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Collaborators and Investigators
Collaborators
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
Publications and helpful links
General 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. doi: 10.1212/01.WNL.0000167384.68207.3E.
- 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. doi: 10.1046/j.1528-1157.2002.45401.x.
- Werhahn KJ, Trinka E, Dobesberger J, Unterberger I, Baum P, Deckert-Schmitz M, Kniess T, Schmitz B, Bernedo V, Ruckes C, Ehrlich A, Kramer G. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia. 2015 Mar;56(3):450-9. doi: 10.1111/epi.12926. Epub 2015 Feb 12.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Epilepsy
- Epilepsies, Partial
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Anticonvulsants
- Sodium Channel Blockers
- Antimanic Agents
- Cytochrome P-450 Enzyme Inducers
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Cytochrome P-450 CYP3A Inducers
- Nootropic Agents
- Lamotrigine
- Levetiracetam
- Carbamazepine
Other Study ID Numbers
- STEPONE05
- ISRCTN: 94839639
- EudraCT Number:2005-003324-19
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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