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Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs (STEP-ONE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00438451
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : February 28, 2013
Last Update Posted : February 28, 2013
Sponsor:
Collaborator:
UCB Pharma GmbH
Information provided by (Responsible Party):
Konrad J. Werhahn, Johannes Gutenberg University Mainz

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Focal Epilepsy
Interventions Drug: Levetiracetam
Drug: Carbamazepine
Drug: Lamotrigine
Enrollment 361
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).
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description

Levetiracetam 250mg: capsules, each containing one Levetiracetam 250mg film-coated tablet.

During titration phase, subjects received 1 capsule in the evening in the first 14 days, 2 capsules (1 in the morning and 1 in the evening) in week 3 and 4, 3 capsules in week 5 (1 in the morning and 2 in the evening) and 4 capsules from week 6 onwards (2 in the morning and 2 in the evening). During maintenance phase, dose adjustments could be made according to tolerability and seizure control in steps of 1 capsule per week. Dosages between 2 to 12 capsules per day were allowed.

Carbamazepine 100mg: capsules, each containing half of one Carbamazepine 200mg slow release tablet.

During titration phase, subjects received 1 capsule in the evening in the first 14 days, 2 capsules (1 in the morning and 1 in the evening) in week 3 and 4, 3 capsules in week 5 (1 in the morning and 2 in the evening) and 4 capsules from week 6 onwards (2 in the morning and 2 in the evening). During maintenance phase, dose adjustments could be made according to tolerability and seizure control in steps of 1 capsule per week. Dosages between 2 to 12 capsules per day were allowed.

Lamotrigine 25mg: capsules, each containing one Lamotrigine 25mg tablet. During titration phase, subjects received 1 capsule in the evening in the first 14 days, 2 capsules (1 in the morning and 1 in the evening) in week 3 and 4, 3 capsules in week 5 (1 in the morning and 2 in the evening) and 4 capsules from week 6 onwards (2 in the morning and 2 in the evening). During maintenance phase, dose adjustments could be made according to tolerability and seizure control in steps of 1 capsule per week. Dosages between 2 to 12 capsules per day were allowed.
Period Title: Overall Study
Started 122 121 118
Safety Population 122 121 117
ITT Population 122 120 117
Maintenance Phase (Week 7-58) 93 89 93
Completed 75 55 65
Not Completed 47 66 53
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine Total
Hide Arm/Group Description Levetiracetam 250mg Carbamazepine 100mg Lamotrigine 25mg Total of all reporting groups
Overall Number of Baseline Participants 122 120 117 359
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 122 participants 120 participants 117 participants 359 participants
71.8  (7.49) 71.7  (6.66) 70.7  (7.43) 71.4  (7.2)
[1]
Measure Description: Age is shown for ITT population
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Female
41
  33.6%
55
  45.8%
48
  41.0%
144
  40.1%
Male
81
  66.4%
65
  54.2%
69
  59.0%
215
  59.9%
[1]
Measure Description: Gender is shown for ITT population
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
122
 100.0%
120
 100.0%
117
 100.0%
359
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Race is shown for ITT population
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Germany 95 92 91 278
Austria 18 18 16 52
Switzerland 9 10 10 29
[1]
Measure Description: Region of enrollment is shown for ITT population
Epilepsy history - number of seizures   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of seizures
Number Analyzed 122 participants 120 participants 117 participants 359 participants
3.8  (9.85) 4.8  (10.78) 2.7  (3.14) 3.75  (8.69)
[1]
Measure Description: is shown for ITT population
Epilepsy history - Aura   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 23 28 21 72
No 99 92 95 286
NA 0 0 1 1
[1]
Measure Description: is shown for ITT population "NA" refer to the fact that the epilepsy history - Aura is unknown
Epilepsy history - Autonomic seizure   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 1 2 0 3
No 121 118 117 356
[1]
Measure Description: is shown for ITT population
Epilepsy history - Dialeptic seizure   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 13 15 18 46
No 109 105 99 313
[1]
Measure Description: is shown for ITT population
Epilepsy history - Motor seizure   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 95 101 95 291
No 27 19 22 68
[1]
Measure Description: is shown for ITT population
Epileptic history - Special seizure   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 8 13 12 33
No 114 107 105 326
[1]
Measure Description: is shown for ITT population
EEG (electroencephalogram) pathological   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 86 84 71 241
No 35 36 45 116
Missing 1 0 1 2
[1]
Measure Description: is shown for ITT population
MRT (Magnetic Resonance Tomograhy) pathological   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 59 63 62 184
No 11 10 13 34
Missing 52 47 42 141
[1]
Measure Description: is shown for ITT population
CCT (Cranial Computed Tomography) pathological   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 122 participants 120 participants 117 participants 359 participants
Yes 76 82 64 222
No 23 19 19 61
Missing 23 19 34 76
[1]
Measure Description: is shown for ITT population
1.Primary Outcome
Title 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment
Hide Description [Not Specified]
Time Frame 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 122 120 117
Mean (95% Confidence Interval)
Unit of Measure: proportion of participants
0.61
(0.53 to 0.70)
0.46
(0.37 to 0.55)
0.56
(0.47 to 0.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0201
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1536
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3615
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0478
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0578
Comments [Not Specified]
Method Regression, Logistic
Comments adjusted for treatment (p=0.0578), country (p=0.4649), pooled sites (p=0.4420) and number of concurrent diseases (p=0.0192)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.838
Confidence Interval (2-Sided) 95%
1.092 to 3.093
Estimation Comments Odds ratio given here is for comparison "LEV vs CBZ": OR=1.838 KI=(1.092-3.093) "LEV vs LTG": OR=1.169 KI=(0.689-1.984) "CBZ vs LTG": OR=0.636 KI=(0.377-1.073) "Number of concurrent diseases": OR=0.921 KI=(0.859-0.987)
2.Secondary Outcome
Title Time to Drop Out
Hide Description number of days between randomization and premature discontinuation of the study
Time Frame 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 122 120 117
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
265 [2] 
(119 to NA)
NA [1] 
(270 to NA)
[1]
less than 50% of patients dropped out
[2]
not enough patients dropped out
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0596
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)
Hide Description Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30.
Time Frame Week 30
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 122 120 117
Measure Type: Number
Unit of Measure: percentage of participants
48 39 49
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2517
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)
Hide Description Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58.
Time Frame week 58
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 122 120 117
Measure Type: Number
Unit of Measure: percentage of participants
43 33 38
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3303
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)
Hide Description [Not Specified]
Time Frame over the whole duration of 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 122 120 117
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(308 to NA)
[1]
could not be estimated since there were less than 50% events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam, Carbamazepine, Lamotrigine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5022
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 75 55 65
Measure Type: Number
Unit of Measure: number of seizures
168 131 130
7.Secondary Outcome
Title Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population who reached the maintenance phase
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 91 87 91
Measure Type: Number
Unit of Measure: proportion of seizure-free days
0.99 0.99 0.99
8.Secondary Outcome
Title QOLIE-31 (Quality Of Life In Epilepsy) Results at V6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population who filled out QOLIE-31 at V6
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 90 90 89
Mean (Standard Deviation)
Unit of Measure: units on a scale
Seizure worry 85.1  (19.89) 75.4  (26.87) 75.0  (26.26)
Overall quality of life 67.2  (21.76) 65.0  (20.65) 67.1  (20.96)
Emotional well-being 72.0  (19.42) 69.8  (18.76) 67.4  (20.25)
Energy/fatigue 60.8  (21.03) 54.5  (21.33) 59.8  (22.07)
Cognitive functioning 75.1  (19.48) 68.9  (20.96) 68.0  (21.11)
Medication effects 77.6  (26.78) 70.6  (28.21) 72.6  (30.34)
Social functioning 81.1  (19.23) 76.3  (25.49) 76.7  (24.28)
Total Score 73.9  (15.89) 68.9  (17.80) 69.1  (17.12)
Health Scale 69.5  (19.28) 65.7  (21.21) 67.5  (19.84)
9.Secondary Outcome
Title Portland Neurotoxicity Scale (PNS) at V6
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population who filled out PNS at V6
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 90 90 89
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cognitive toxicity subscore 22.2  (12.52) 27.3  (15.71) 23.7  (11.44)
Somatomotor subscore 10.5  (5.53) 11.4  (6.96) 10.8  (5.42)
Total Score 32.7  (16.81) 38.7  (21.73) 34.5  (15.67)
10.Secondary Outcome
Title Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population who had data at V6
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 84 84 85
Mean (Standard Deviation)
Unit of Measure: units on a scale
26.0  (7.22) 26.0  (7.05) 25.4  (6.82)
11.Secondary Outcome
Title Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6
Hide Description

Evaluation of current testing at V6:

≥29 score points: Inconspicuous; 26 to 28 score points: Borderline;

≤25 score points: Impaired

Time Frame 58 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population with data at V6
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 84 84 85
Measure Type: Number
Unit of Measure: participants
Without pathological findings 38 34 31
Borderline 10 17 15
Impaired 36 33 39
12.Secondary Outcome
Title Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of ITT population with data at V6 and V0
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description:
Levetiracetam 250mg
Carbamazepine 100mg
Lamotrigine 25mg
Overall Number of Participants Analyzed 82 80 81
Measure Type: Number
Unit of Measure: participants
Improved 15 16 15
Unchanged 61 56 53
Worsened 6 8 13
Time Frame Adverse events were recorded from day 1 of treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Levetiracetam Carbamazepine Lamotrigine
Hide Arm/Group Description Levetiracetam 250mg Carbamazepine 100mg Lamotrigine 25mg
All-Cause Mortality
Levetiracetam Carbamazepine Lamotrigine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Levetiracetam Carbamazepine Lamotrigine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   33/122 (27.05%)      36/121 (29.75%)      32/117 (27.35%)    
Blood and lymphatic system disorders       
Iron deficiency anaemia * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Cardiac disorders       
Acute coronary syndrome * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 0/117 (0.00%)  0
Acute mycardial infarction * 1  2/122 (1.64%)  2 0/121 (0.00%)  0 1/117 (0.85%)  1
Angina pectoris * 1  0/122 (0.00%)  0 0/121 (0.00%)  1 1/117 (0.85%)  1
Cardiac failure acute * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Coronary artery disease * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Coronary artery occlusion * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Myocardial infarction * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 1/117 (0.85%)  1
Ear and labyrinth disorders       
Deafness unilateral * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Vertigo * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Eye disorders       
Macular hole * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Visual impairment * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Gastrointestinal disorders       
Abdominal discomfort * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Colitis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Diarrhoea * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Gastric ulcer perforation * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Gastritis * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Gastrointestinal disorder * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Gastrointestinal haemorrhage * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Intestinal ischaemia * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Nausea * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Pancreatitis acute * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Subileus * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 1/117 (0.85%)  1
Vomiting * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
General disorders       
Death * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 0/117 (0.00%)  0
Facial pain * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Gait disturbance * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Hernia * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Pain * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Hepatobiliary disorders       
Bile duct stone * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Cholecystitis acute * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Hepatitis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Immune system disorders       
Drug hypersensitivity * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Infections and infestations       
Bacterial infection * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Bronchopneumonia * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Gastroenteritis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 1/117 (0.85%)  1
Herpes zoster * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Infection * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Infectious peritonitis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Pneumonia * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 1/117 (0.85%)  1
Urinary tract infection * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 2/117 (1.71%)  2
Injury, poisoning and procedural complications       
Alcohol poisoning * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Cervical vertebral fracture * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Contusion * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Craniocerebral injury * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Fall * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Hand fracture * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
In-stent coronary artery restenosis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
In-stent coronary artery restenosis * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Lumbar vertebral fracture * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Meniscus lesion * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Radius fracture * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Thoracic vertebral fracture * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Upper limb fracture * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Investigations       
Arthroscopy * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Blood potassium decreased * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Blood sodium decreased * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 0/117 (0.00%)  0
Helicobacter test positive * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Hepatic enzyme increased * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Weight decreased * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Metabolism and nutrition disorders       
Hyponatraemia * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Bursitis * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Systemic lupus erythematosus * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Anaplastic astrocytoma * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Brain neoplasm * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Colon cancer * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Malignant melanoma * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Metastatic bronchial carcinoma * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Renal cancer * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Nervous system disorders       
Amnestic disorder * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Brain stem infarction * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Carotid artery stenosis * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Cerebral haemorrhage * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 1/117 (0.85%)  1
Cerebral infarction * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Cerebral ischaemia * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Cerebrovascular accident * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Complex partial seizures * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 1/117 (0.85%)  1
Convulsion * 1  0/122 (0.00%)  0 2/121 (1.65%)  2 0/117 (0.00%)  0
Dementia * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Dizziness * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Epilepsy * 1  4/122 (3.28%)  4 1/121 (0.83%)  1 0/117 (0.00%)  0
Grand mal convulsion * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 5/117 (4.27%)  7
Headache * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 1/117 (0.85%)  1
Hemiparesis * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 0/117 (0.00%)  0
Loss of consciousness * 1  2/122 (1.64%)  2 0/121 (0.00%)  0 0/117 (0.00%)  0
Memory impairment * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Partial seizures * 1  2/122 (1.64%)  2 0/121 (0.00%)  0 0/117 (0.00%)  0
Partial seizures with secondary generalisation * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Speech disorder * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Status epilepticus * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Stupor * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Transient ischaemic attack * 1  1/122 (0.82%)  2 0/121 (0.00%)  0 1/117 (0.85%)  1
Psychiatric disorders       
Completed suicide * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Confusional state * 1  1/122 (0.82%)  1 1/121 (0.83%)  1 1/117 (0.85%)  1
Delirium * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Depression * 1  2/122 (1.64%)  2 0/121 (0.00%)  0 0/117 (0.00%)  0
Suicidal behavior * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Renal and urinary disorders       
Renal failure acute * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 1/117 (0.85%)  1
Reproductive system and breast disorders       
Benign prostatic hyperplasia * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 1/117 (0.85%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Pulmonary embolism * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 2/117 (1.71%)  2
Sleep apnoea syndrome * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis allergic * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Petechiae * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Skin ulcer * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Purpura * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Surgical and medical procedures       
Bursa removal * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Cataract operation * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Meningioma surgery * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Radiotherapy * 1  0/122 (0.00%)  0 0/121 (0.00%)  0 1/117 (0.85%)  1
Vascular disorders       
Deep vein thrombosis * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
Hypertension * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Hypertensive crisis * 1  0/122 (0.00%)  0 1/121 (0.83%)  1 0/117 (0.00%)  0
Temporal arteritis * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 0/117 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levetiracetam Carbamazepine Lamotrigine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   108/122 (88.52%)      108/121 (89.26%)      110/117 (94.02%)    
Gastrointestinal disorders       
Constipation * 1  2/122 (1.64%)  2 15/121 (12.40%)  16 5/117 (4.27%)  5
Diarrhoea * 1  9/122 (7.38%)  11 13/121 (10.74%)  14 14/117 (11.97%)  17
Dry mouth * 1  1/122 (0.82%)  1 5/121 (4.13%)  5 7/117 (5.98%)  8
Nausea * 1  11/122 (9.02%)  15 18/121 (14.88%)  21 17/117 (14.53%)  23
Vomiting * 1  5/122 (4.10%)  10 6/121 (4.96%)  11 7/117 (5.98%)  7
General disorders       
Fatigue * 1  31/122 (25.41%)  48 46/121 (38.02%)  51 23/117 (19.66%)  29
Gait disturbance * 1  8/122 (6.56%)  8 10/121 (8.26%)  11 5/117 (4.27%)  6
Infections and infestations       
Bronchitis * 1  0/122 (0.00%)  0 2/121 (1.65%)  2 7/117 (5.98%)  7
Nasopharyngitis * 1  20/122 (16.39%)  26 13/121 (10.74%)  18 8/117 (6.84%)  10
Urinary tract infection * 1  3/122 (2.46%)  3 6/121 (4.96%)  6 1/117 (0.85%)  1
Injury, poisoning and procedural complications       
Fall * 1  1/122 (0.82%)  1 5/121 (4.13%)  7 6/117 (5.13%)  6
Investigations       
Gamma-glutamyltransferase increased * 1  4/122 (3.28%)  4 18/121 (14.88%)  20 5/117 (4.27%)  5
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  7/122 (5.74%)  7 6/121 (4.96%)  7 10/117 (8.55%)  14
Back pain * 1  9/122 (7.38%)  11 4/121 (3.31%)  4 7/117 (5.98%)  8
Myalgia * 1  2/122 (1.64%)  2 3/121 (2.48%)  3 8/117 (6.84%)  9
Pain in extremity * 1  8/122 (6.56%)  8 2/121 (1.65%)  2 7/117 (5.98%)  12
Nervous system disorders       
Convulsion * 1  5/122 (4.10%)  5 7/121 (5.79%)  9 11/117 (9.40%)  23
Dizziness * 1  35/122 (28.69%)  52 31/121 (25.62%)  35 36/117 (30.77%)  44
Epilepsy * 1  19/122 (15.57%)  35 11/121 (9.09%)  16 14/117 (11.97%)  22
Grand mal convulsion * 1  1/122 (0.82%)  1 0/121 (0.00%)  0 7/117 (5.98%)  14
Headache * 1  31/122 (25.41%)  46 29/121 (23.97%)  39 29/117 (24.79%)  44
Memory impairment * 1  5/122 (4.10%)  6 7/121 (5.79%)  7 5/117 (4.27%)  6
Partial seizures * 1  1/122 (0.82%)  3 5/121 (4.13%)  19 8/117 (6.84%)  10
Tremor * 1  6/122 (4.92%)  6 5/121 (4.13%)  6 6/117 (5.13%)  10
Sleep disorder * 1  4/122 (3.28%)  5 5/121 (4.13%)  5 9/117 (7.69%)  10
Psychiatric disorders       
Depression * 1  4/122 (3.28%)  5 6/121 (4.96%)  6 4/117 (3.42%)  4
Renal and urinary disorders       
Renal failure * 1  9/122 (7.38%)  9 0/121 (0.00%)  0 8/117 (6.84%)  8
Respiratory, thoracic and mediastinal disorders       
Cough * 1  9/122 (7.38%)  10 9/121 (7.44%)  9 8/117 (6.84%)  8
Skin and subcutaneous tissue disorders       
Pruritus * 1  5/122 (4.10%)  5 10/121 (8.26%)  10 9/117 (7.69%)  9
Rash * 1  7/122 (5.74%)  7 6/121 (4.96%)  8 2/117 (1.71%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
This study was supported (as investigator-initated trial) by an educational grant from UCB GmbH, Germany. A disclosure restriction applies on the PI in that UCB can review results communications prior to public release and can embargo communications regarding trial results for a period of 90 days from the time submitted. As of Jan-01-2012 the study chair is an employee to UCB Biosciences GmbH working as Medical Director in the Therapeutic Area CNS within Global Projects and Development.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: C. Ruckes
Organization: Interdisciplinary Center for Clinical Trials (IZKS Mainz)
Phone: +49 (0) 6131 17 ext 9919
EMail: ruckes@izks-mainz.de
Layout table for additonal information
Responsible Party: Konrad J. Werhahn, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT00438451     History of Changes
Other Study ID Numbers: STEPONE05
ISRCTN: 94839639
EudraCT Number:2005-003324-19
First Submitted: February 21, 2007
First Posted: February 22, 2007
Results First Submitted: September 24, 2012
Results First Posted: February 28, 2013
Last Update Posted: February 28, 2013