Focal Epilepsy
Conditions
Keywords
elderly, focal epilepsy, anticonvulsive, treatment, levetiracetam, lamotrigine, carbamazepine
Brief summary
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.
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).
Interventions
DRUGLamotrigine
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.
DRUGLevetiracetam
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.
DRUGCarbamazepine
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.
Sponsors
UCB Pharma GmbH
Johannes Gutenberg University Mainz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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 | 58 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase | 52 weeks | — |
| Time to Drop Out | 58 weeks | number of days between randomization and premature discontinuation of the study |
| Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4) | Week 30 | Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30. |
| Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6) | week 58 | Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58. |
| The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment) | over the whole duration of 58 weeks | — |
| The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58) | over 52 weeks | 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. |
| Portland Neurotoxicity Scale (PNS) at V6 | at week 58 | 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. |
| Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6 | week 58 | 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. |
| Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | 58 weeks | Evaluation of current testing at V6: ≥29 score points: Inconspicuous; 26 to 28 score points: Borderline; ≤25 score points: Impaired |
| Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | week 58 | 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 |
| QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | 58 weeks, final visit | 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. |
Countries
Germany
Participant flow
Recruitment details
43 study centres in three countries participated in this study (31 in Germany, 5 in Austria, 7 in Switzerland). The number of patients recruited in each country (242 Germany, 55 Austria, 29 Switzerland) and per centre (range from 1 to 53) was heterogeneous. Therefore, centre effects were explored by pooling the centres with less than 20 subjects.
Pre-assignment details
In total, 361 patients were randomized. 359 patients were analysed ITT (patient 0213 did not suffer from epilepsy, patient 3604 should not have been asked for informed consent, because of his legal guardianship).
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Levetiracetam 250mg | 122 |
| Carbamazepine Carbamazepine 100mg | 120 |
| Lamotrigine Lamotrigine 25mg | 117 |
| Total | 359 |
Baseline characteristics
| Characteristic | Levetiracetam | Carbamazepine | Lamotrigine | Total |
|---|---|---|---|---|
| Age Continuous | 71.8 years STANDARD_DEVIATION 7.49 | 71.7 years STANDARD_DEVIATION 6.66 | 70.7 years STANDARD_DEVIATION 7.43 | 71.4 years STANDARD_DEVIATION 7.2 |
| CCT (Cranial Computed Tomography) pathological Missing | 23 participants | 19 participants | 34 participants | 76 participants |
| CCT (Cranial Computed Tomography) pathological No | 23 participants | 19 participants | 19 participants | 61 participants |
| CCT (Cranial Computed Tomography) pathological Yes | 76 participants | 82 participants | 64 participants | 222 participants |
| EEG (electroencephalogram) pathological Missing | 1 participants | 0 participants | 1 participants | 2 participants |
| EEG (electroencephalogram) pathological No | 35 participants | 36 participants | 45 participants | 116 participants |
| EEG (electroencephalogram) pathological Yes | 86 participants | 84 participants | 71 participants | 241 participants |
| Epilepsy history - Aura NA | 0 participants | 0 participants | 1 participants | 1 participants |
| Epilepsy history - Aura No | 99 participants | 92 participants | 95 participants | 286 participants |
| Epilepsy history - Aura Yes | 23 participants | 28 participants | 21 participants | 72 participants |
| Epilepsy history - Autonomic seizure No | 121 participants | 118 participants | 117 participants | 356 participants |
| Epilepsy history - Autonomic seizure Yes | 1 participants | 2 participants | 0 participants | 3 participants |
| Epilepsy history - Dialeptic seizure No | 109 participants | 105 participants | 99 participants | 313 participants |
| Epilepsy history - Dialeptic seizure Yes | 13 participants | 15 participants | 18 participants | 46 participants |
| Epilepsy history - Motor seizure No | 27 participants | 19 participants | 22 participants | 68 participants |
| Epilepsy history - Motor seizure Yes | 95 participants | 101 participants | 95 participants | 291 participants |
| Epilepsy history - number of seizures | 3.8 number of seizures STANDARD_DEVIATION 9.85 | 4.8 number of seizures STANDARD_DEVIATION 10.78 | 2.7 number of seizures STANDARD_DEVIATION 3.14 | 3.75 number of seizures STANDARD_DEVIATION 8.69 |
| Epileptic history - Special seizure No | 114 participants | 107 participants | 105 participants | 326 participants |
| Epileptic history - Special seizure Yes | 8 participants | 13 participants | 12 participants | 33 participants |
| MRT (Magnetic Resonance Tomograhy) pathological Missing | 52 participants | 47 participants | 42 participants | 141 participants |
| MRT (Magnetic Resonance Tomograhy) pathological No | 11 participants | 10 participants | 13 participants | 34 participants |
| MRT (Magnetic Resonance Tomograhy) pathological Yes | 59 participants | 63 participants | 62 participants | 184 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 122 Participants | 120 Participants | 117 Participants | 359 Participants |
| Region of Enrollment Austria | 18 participants | 18 participants | 16 participants | 52 participants |
| Region of Enrollment Germany | 95 participants | 92 participants | 91 participants | 278 participants |
| Region of Enrollment Switzerland | 9 participants | 10 participants | 10 participants | 29 participants |
| Sex: Female, Male Female | 41 Participants | 55 Participants | 48 Participants | 144 Participants |
| Sex: Female, Male Male | 81 Participants | 65 Participants | 69 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 108 / 122 | 108 / 121 | 110 / 117 |
| serious Total, serious adverse events | 33 / 122 | 36 / 121 | 32 / 117 |
Outcome results
Primary
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
Population: ITT population:~All randomized patients were included in the Intention-to-Treat (ITT) population except patients that were not evaluable for efficacy e.g. patients without epilepsy or patients not able to comply with the study requirements.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Levetiracetam | 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment | 0.61 proportion of participants |
| Carbamazepine | 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment | 0.46 proportion of participants |
| Lamotrigine | 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment | 0.56 proportion of participants |
p-value: 0.3615Fisher Exact
p-value: 0.0478Fisher Exact
p-value: 0.0201Fisher Exact
p-value: 0.1536Fisher Exact
p-value: 0.057895% CI: [1.092, 3.093]Regression, Logistic
Secondary
Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)
Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30.
Time frame: Week 30
Population: ITT population:~All randomized patients were included in the Intention-to-Treat (ITT) population except patients that were not evaluable for efficacy e.g. patients without epilepsy or patients not able to comply with the study requirements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4) | 48 percentage of participants |
| Carbamazepine | Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4) | 39 percentage of participants |
| Lamotrigine | Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4) | 49 percentage of participants |
p-value: 0.2517Fisher Exact
Secondary
Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)
Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58.
Time frame: week 58
Population: ITT population:~All randomized patients were included in the Intention-to-Treat (ITT) population except patients that were not evaluable for efficacy e.g. patients without epilepsy or patients not able to comply with the study requirements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6) | 43 percentage of participants |
| Carbamazepine | Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6) | 33 percentage of participants |
| Lamotrigine | Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6) | 38 percentage of participants |
p-value: 0.3303Fisher Exact
Secondary
Portland Neurotoxicity Scale (PNS) at V6
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.
Time frame: at week 58
Population: Patients of ITT population who filled out PNS at V6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | Portland Neurotoxicity Scale (PNS) at V6 | Somatomotor subscore | 10.5 units on a scale | Standard Deviation 5.53 |
| Levetiracetam | Portland Neurotoxicity Scale (PNS) at V6 | Cognitive toxicity subscore | 22.2 units on a scale | Standard Deviation 12.52 |
| Levetiracetam | Portland Neurotoxicity Scale (PNS) at V6 | Total Score | 32.7 units on a scale | Standard Deviation 16.81 |
| Carbamazepine | Portland Neurotoxicity Scale (PNS) at V6 | Somatomotor subscore | 11.4 units on a scale | Standard Deviation 6.96 |
| Carbamazepine | Portland Neurotoxicity Scale (PNS) at V6 | Cognitive toxicity subscore | 27.3 units on a scale | Standard Deviation 15.71 |
| Carbamazepine | Portland Neurotoxicity Scale (PNS) at V6 | Total Score | 38.7 units on a scale | Standard Deviation 21.73 |
| Lamotrigine | Portland Neurotoxicity Scale (PNS) at V6 | Cognitive toxicity subscore | 23.7 units on a scale | Standard Deviation 11.44 |
| Lamotrigine | Portland Neurotoxicity Scale (PNS) at V6 | Total Score | 34.5 units on a scale | Standard Deviation 15.67 |
| Lamotrigine | Portland Neurotoxicity Scale (PNS) at V6 | Somatomotor subscore | 10.8 units on a scale | Standard Deviation 5.42 |
Secondary
Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase
Time frame: 52 weeks
Population: Patients of ITT population who reached the maintenance phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase | 0.99 proportion of seizure-free days |
| Carbamazepine | Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase | 0.99 proportion of seizure-free days |
| Lamotrigine | Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase | 0.99 proportion of seizure-free days |
Secondary
QOLIE-31 (Quality Of Life In Epilepsy) Results at V6
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.
Time frame: 58 weeks, final visit
Population: Patients of ITT population who filled out QOLIE-31 at V6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Energy/fatigue | 60.8 units on a scale | Standard Deviation 21.03 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Health Scale | 69.5 units on a scale | Standard Deviation 19.28 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Medication effects | 77.6 units on a scale | Standard Deviation 26.78 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Cognitive functioning | 75.1 units on a scale | Standard Deviation 19.48 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Seizure worry | 85.1 units on a scale | Standard Deviation 19.89 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Total Score | 73.9 units on a scale | Standard Deviation 15.89 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Emotional well-being | 72.0 units on a scale | Standard Deviation 19.42 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Overall quality of life | 67.2 units on a scale | Standard Deviation 21.76 |
| Levetiracetam | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Social functioning | 81.1 units on a scale | Standard Deviation 19.23 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Cognitive functioning | 68.9 units on a scale | Standard Deviation 20.96 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Seizure worry | 75.4 units on a scale | Standard Deviation 26.87 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Overall quality of life | 65.0 units on a scale | Standard Deviation 20.65 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Emotional well-being | 69.8 units on a scale | Standard Deviation 18.76 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Energy/fatigue | 54.5 units on a scale | Standard Deviation 21.33 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Medication effects | 70.6 units on a scale | Standard Deviation 28.21 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Social functioning | 76.3 units on a scale | Standard Deviation 25.49 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Total Score | 68.9 units on a scale | Standard Deviation 17.8 |
| Carbamazepine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Health Scale | 65.7 units on a scale | Standard Deviation 21.21 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Emotional well-being | 67.4 units on a scale | Standard Deviation 20.25 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Seizure worry | 75.0 units on a scale | Standard Deviation 26.26 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Social functioning | 76.7 units on a scale | Standard Deviation 24.28 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Overall quality of life | 67.1 units on a scale | Standard Deviation 20.96 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Health Scale | 67.5 units on a scale | Standard Deviation 19.84 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Cognitive functioning | 68.0 units on a scale | Standard Deviation 21.11 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Energy/fatigue | 59.8 units on a scale | Standard Deviation 22.07 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Total Score | 69.1 units on a scale | Standard Deviation 17.12 |
| Lamotrigine | QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 | Medication effects | 72.6 units on a scale | Standard Deviation 30.34 |
Secondary
Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6
Evaluation of current testing at V6: ≥29 score points: Inconspicuous; 26 to 28 score points: Borderline; ≤25 score points: Impaired
Time frame: 58 weeks
Population: Patients of ITT population with data at V6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Borderline | 10 participants |
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Without pathological findings | 38 participants |
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Impaired | 36 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Borderline | 17 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Without pathological findings | 34 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Impaired | 33 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Without pathological findings | 31 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Impaired | 39 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 | Borderline | 15 participants |
Secondary
Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6)
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
Time frame: week 58
Population: Patients of ITT population with data at V6 and V0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Unchanged | 61 participants |
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Improved | 15 participants |
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Worsened | 6 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Unchanged | 56 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Improved | 16 participants |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Worsened | 8 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Improved | 15 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Worsened | 13 participants |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) | Unchanged | 53 participants |
Secondary
Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6
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.
Time frame: week 58
Population: Patients of ITT population who had data at V6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6 | 26.0 units on a scale | Standard Deviation 7.22 |
| Carbamazepine | Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6 | 26.0 units on a scale | Standard Deviation 7.05 |
| Lamotrigine | Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6 | 25.4 units on a scale | Standard Deviation 6.82 |
Secondary
The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)
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.
Time frame: over 52 weeks
Population: Completer population:~The completer population comprises all patients still being in the study at week 58 (This definition deviates minimally from the protocol. It could not be assessed from the CRF data, if patients were on treatment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58) | 168 number of seizures |
| Carbamazepine | The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58) | 131 number of seizures |
| Lamotrigine | The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58) | 130 number of seizures |
Secondary
The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)
Time frame: over the whole duration of 58 weeks
Population: ITT population:~All randomized patients were included in the Intention-to-Treat (ITT) population except patients that were not evaluable for efficacy e.g. patients without epilepsy or patients not able to comply with the study requirements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam | The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment) | NA days |
| Carbamazepine | The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment) | NA days |
| Lamotrigine | The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment) | NA days |
p-value: 0.5022Log Rank
Secondary
Time to Drop Out
number of days between randomization and premature discontinuation of the study
Time frame: 58 weeks
Population: ITT population:~All randomized patients were included in the Intention-to-Treat (ITT) population except patients that were not evaluable for efficacy e.g. patients without epilepsy or patients not able to comply with the study requirements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam | Time to Drop Out | NA days |
| Carbamazepine | Time to Drop Out | 265 days |
| Lamotrigine | Time to Drop Out | NA days |
p-value: 0.0596Log Rank