Trial Outcomes & Findings for Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures (NCT NCT00152516)

NCT ID: NCT00152516

Last Updated: 2013-02-12

Results Overview

Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

255 participants

Primary outcome timeframe

Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Results posted on

2013-02-12

Participant Flow

102 sites in 17 countries participated in the study, of which 85 sites in 16 countries enrolled subjects in the study. First subject enrolled: 23 October 2004, Last subject last visit: 24 June 2008

Protocol amendment C2 (August 7, 2006) allowed direct enrollment from India, Australia, and New Zealand bypassing the blinded feeder studies N01009 and N01103.

Participant milestones

Participant milestones
Measure
Levetiracetam
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Overall Study
STARTED
255
Overall Study
COMPLETED
180
Overall Study
NOT COMPLETED
75

Reasons for withdrawal

Reasons for withdrawal
Measure
Levetiracetam
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Overall Study
Adverse Event
18
Overall Study
Lack and Loss of Efficacy
30
Overall Study
Lost to Follow-up
5
Overall Study
Withdrawal by Subject
8
Overall Study
Protocol Violation
3
Overall Study
Other: Mother Refused To Cooperate
1
Overall Study
Other: Given Commercial Drug in Error
2
Overall Study
Other: Parents Withdrew Consent
2
Overall Study
Other: Non-Compliance
2
Overall Study
Other: Primary Care Physician's Decision
1
Overall Study
Other: Moved Out Of State
1
Overall Study
Other: Underwent Surgery for Epilepsy
1
Overall Study
Other: Sz Worsening, Seeking 2nd Opinion
1

Baseline Characteristics

Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Levetiracetam
n=255 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Age, Categorical
<=18 years
255 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Age Continuous
5.28 years
STANDARD_DEVIATION 4.69 • n=5 Participants
Sex: Female, Male
Female
116 Participants
n=5 Participants
Sex: Female, Male
Male
139 Participants
n=5 Participants
Region of Enrollment
United States
123 participants
n=5 Participants
Region of Enrollment
Russian Federation
7 participants
n=5 Participants
Region of Enrollment
Italy
6 participants
n=5 Participants
Region of Enrollment
United Kingdom
2 participants
n=5 Participants
Region of Enrollment
India
20 participants
n=5 Participants
Region of Enrollment
France
7 participants
n=5 Participants
Region of Enrollment
Czech Republic
9 participants
n=5 Participants
Region of Enrollment
Hungary
4 participants
n=5 Participants
Region of Enrollment
Mexico
6 participants
n=5 Participants
Region of Enrollment
Canada
11 participants
n=5 Participants
Region of Enrollment
Poland
2 participants
n=5 Participants
Region of Enrollment
Brazil
29 participants
n=5 Participants
Region of Enrollment
Belgium
4 participants
n=5 Participants
Region of Enrollment
Romania
7 participants
n=5 Participants
Region of Enrollment
South Africa
7 participants
n=5 Participants
Region of Enrollment
Germany
11 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 4 were missing a baseline, 3 had a baseline of 0, and 1 was missing treatment period seizure data. The result was a sample size of 247. Of these 247 subjects 226 continued into the maintenance period.

Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=247 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Percentage Change (Reduction) of Partial (Type I) Seizure Frequency Per Week From Baseline Over Time During Treatment Period.
Up-titration/Conversion
51.06 percent reduction in seizures Per Week
Interval -10.7 to 91.59
Percentage Change (Reduction) of Partial (Type I) Seizure Frequency Per Week From Baseline Over Time During Treatment Period.
Maintenance
68.87 percent reduction in seizures Per Week
Interval -3.6 to 96.61

SECONDARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 4 were missing a baseline, 2 had a baseline of 0, and 1 was missing treatment period seizure data. The result was a sample size of 248. Of these 248 subjects 227 continued into the maintenance period.

Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=248 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Percentage Change (Reduction) of Total (Type I, II, III) Seizure Frequency Per Week From Baseline Over Time During Treatment Period.
Up-titration/Conversion Period
47.44 Percent Reduction in Seizures per Week
Interval -21.18 to 88.7
Percentage Change (Reduction) of Total (Type I, II, III) Seizure Frequency Per Week From Baseline Over Time During Treatment Period.
Maintenance Period
66.02 Percent Reduction in Seizures per Week
Interval -3.98 to 95.0

SECONDARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 1 was missing treatment period seizure data leaving a sample size of 254. Of these 254 subjects 233 continued into the maintenance period.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=254 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period.
Up-titration/Conversion Period
2.85 Seizures Per Week
Interval 0.23 to 26.3
Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period.
Maintenance Period
1.49 Seizures Per Week
Interval 0.07 to 17.89

SECONDARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 1 was missing treatment period seizure data leaving a sample size of 254. Of these 254 subjects 233 continued into the maintenance period.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=254 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period.
Up-titration/Conversion Period
3.15 Seizures Per Week
Interval 0.25 to 31.17
Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period.
Maintenance Period
1.91 Seizures Per Week
Interval 0.09 to 24.86

SECONDARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 4 were missing a baseline and 1 was missing treatment period seizure data. The result was a sample size of 250. Of these 250 subjects 229 continued into the maintenance period.

Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=250 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Change (Reduction) From Baseline in Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period
Up-titration/Conversion Period
0.72 Seizures Per Week
Interval -0.81 to 7.14
Change (Reduction) From Baseline in Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period
Maintenance Period
0.93 Seizures Per Week
Interval -0.33 to 8.99

SECONDARY outcome

Timeframe: Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 4 were missing a baseline and 1 was missing treatment period seizure data. The result was a sample size of 250. Of these 250 subjects 229 continued into the maintenance period.

Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=250 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Change (Reduction) From Baseline in Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period
Up-titration/Conversion Period
0.69 Seizures Per Week
Interval -0.89 to 7.84
Change (Reduction) From Baseline in Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period
Maintenance Period
0.93 Seizures Per Week
Interval -0.33 to 10.7

SECONDARY outcome

Timeframe: Up-titration (4 weeks); Maintenance Visits 3-4 (weeks 4-14, 6-15, or 8-16); Visits 4-5 (weeks 14-24, 15-24, or 16-24); Visits 5-6 (weeks 24-36); Visits 6-7 (weeks 36-48)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 4 were missing a baseline, 3 had a baseline of 0, and 1 was missing treatment period seizure data. The result was a sample size of 247. Of these 247 subjects 226 continued into the maintenance period.

The responder rate is defined as the number of responders. A responder is a patient with a 50% or greater change (reduction) in partial seizure frequency per week. Note: Rates were reported as percentages.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=247 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase
Up-titration/Conversion (4 weeks)
50.6 Percentage of Participants
Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase
Maintenance Visits 3-4 (weeks 4-14, 6-15, or 8-16)
59.8 Percentage of Participants
Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase
Maint. Visits 4-5 (weeks 14-24, 15-24, or 16-24);
65.5 Percentage of Participants
Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase
Maintenance Visits 5-6 (weeks 24-36)
68.2 Percentage of Participants
Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase
Maintenance Visits 6-7 (weeks 36-48)
71.8 Percentage of Participants

SECONDARY outcome

Timeframe: Subjects with up to 24 weeks of exposure

Population: Intention to Treat (ITT) subjects with \<= 24 Weeks of Exposure and treatment period seizure data

For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=51 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More)
0.00 Percentage of Days
Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Subjects with greater than 24 weeks of exposure

Population: Intention to Treat (ITT) Subjects with \> 24 Weeks of Exposure and treatment period seizure data

For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=203 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More)
61.49 Percentage of days
Interval 0.0 to 94.07

SECONDARY outcome

Timeframe: Subjects with up to 24 weeks of exposure

Population: Intention to Treat (ITT) Subjects with \<= 24 Weeks of Exposure and treatment period seizure data

For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=51 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More)
0.00 Percentage of Days
Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Subjects with greater than 24 weeks of exposure

Population: Intention to Treat (ITT) subjects with \> 24 weeks of exposure and treatment period seizure data

For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=203 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More)
58.41 Percentage of Days
Interval 0.0 to 93.81

SECONDARY outcome

Timeframe: greater than or equal to 24 weeks, greater than or equal to 40 weeks

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 1 was missing treatment period seizure data leaving a sample size of 254. Of these 254 subjects 233 continued into the maintenance period.

The measure description is the product limit adjusted percent of subjects seizure free starting from the beginning of the Maintenance Period. The up-titration period is the up to 6 week period of increasing dose prior to the Maintenance Period. The Maintenance Period is the period of stable dosing, subsquent to the up-titration period, which could last from 42 to 48 weeks.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=233 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Total Seizure (Type I, II, III) Continuously Seizure Free During the Maintenance Period
>= 24 Weeks
16.5 Percentage of Participants
Total Seizure (Type I, II, III) Continuously Seizure Free During the Maintenance Period
>= 40 Weeks
14.7 Percentage of Participants

SECONDARY outcome

Timeframe: Evaluation period (48 weeks)

Population: 255 subjects were Intention to Treat (ITT), i.e. all subjects with at least 1 dose of study medication. Of these 255 ITT subjects 1 was missing treatment period seizure data.

Type I Seizure is a partial onset Seizure (see International League Against Epilepsy definitions). Type II Seizure is a Generalized Seizure (see International League Against Epilepsy definitions). Type III Seizure is a Unknown Seizure Type (see International League Against Epilepsy definitions). A subject could experience more than one seizure type.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=254 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Percent of Subjects With Each Seizure Type During the Evaluation Period
Type I
88.6 Percentage of Participants
Percent of Subjects With Each Seizure Type During the Evaluation Period
Type II
12.9 Percentage of Participants
Percent of Subjects With Each Seizure Type During the Evaluation Period
Type III
7.1 Percentage of Participants

SECONDARY outcome

Timeframe: End of Evaluation period (week 48 or at point of early discontinuation)

Population: Intention to Treat (ITT) subjects for whom the assessment was performed

There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

Outcome measures

Outcome measures
Measure
Levetiracetam
n=222 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Investigator Global Evaluation Scale
Improved
76.1 Percentage of Participants
Investigator Global Evaluation Scale
No Change
15.3 Percentage of Participants
Investigator Global Evaluation Scale
Worsened
8.6 Percentage of Participants

SECONDARY outcome

Timeframe: End of Evaluation period (week 48 or at point of early discontinuation)

Population: Intention to Treat (ITT) subjects for whom the assessment was performed

There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

Outcome measures

Outcome measures
Measure
Levetiracetam
n=214 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Parent/Guardian Global Evaluation Scale
Improved
75.7 Percentage of Participants
Parent/Guardian Global Evaluation Scale
No Change
12.6 Percentage of Participants
Parent/Guardian Global Evaluation Scale
Worsened
11.7 Percentage of Participants

SECONDARY outcome

Timeframe: End of Evaluation period (week 48 or at point of early discontinuation)

Population: Intention to Treat (ITT) subjects \>= 8 years old for whom the assessment was performed

There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change).

Outcome measures

Outcome measures
Measure
Levetiracetam
n=71 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Subject (>=8 Years Old) Global Evaluation Scale
Improved
78.9 Percentage of Participants
Subject (>=8 Years Old) Global Evaluation Scale
No Change
15.5 Percentage of Participants
Subject (>=8 Years Old) Global Evaluation Scale
Worsened
5.6 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Visit 5 (Week 24) and Visit 7 (Week 48)

Population: At baseline there were 98 subjects with valid Memory Screen composite scores (mean=85.5, standard deviation=18.7). Of these 98 subjects, 87 had valid scores at Visit 5 (week 24) and 80 at Visit 7 (week 48).

The Leiter-R AM battery has 10 subtests. The raw scores of the subtests are converted into scaled scores. Six composite scores are constructed from the 10 subtest scaled scores. The Memory Screen is one of them. It is composed of 2 subtests the Associated Pairs and Forward Memory. The sum of the Associated Pairs and Forward Memory subtest scaled scores are converted into a Memory composite score normally distributed with a mean and standard deviation of 100 (±15). Higher scores and positive changes from baseline are better. The range of the Memory Screen composite score is 44 to 155.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=87 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Leiter-R Associated Memory (AM) Memory Screen Composite Score Change From Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) (4 to 16 Year Olds)
Visit 5 (week 24)
4.8 Score on a scale
Standard Deviation 12.6
Leiter-R Associated Memory (AM) Memory Screen Composite Score Change From Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) (4 to 16 Year Olds)
Visit 7 (week 48)
4.5 Score on a scale
Standard Deviation 15.3

SECONDARY outcome

Timeframe: Visit 5 (Week 24)

Population: The Bayley Scale of Infant Development (BSID) II assessment was performed only at selected sites where a neuropsychologist was available. Both a valid baseline and Visit 5 (week 24) assessment had to be present.

This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (\>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (\<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=30 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Olds)
Worsened
5 Number of subjects
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Olds)
Stable
21 Number of subjects
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Olds)
Improved
4 Number of subjects

SECONDARY outcome

Timeframe: Visit 7 (week 48)

Population: The Bayley Scale of Infant Development (BSID) II assessment was performed only at selected sites where a neuropsychologist was available. Both a valid baseline and Visit 7 (week 48) assessment had to be present.

This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (\>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (\<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=25 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Olds)
Worsened
7 Number of subjects
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Olds)
Stable
17 Number of subjects
Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Olds)
Improved
1 Number of subjects

SECONDARY outcome

Timeframe: Visit 5 (week 24)

Population: The Bayley Scale of Infant Development (BSID) II assessment was performed only at selected sites where a neuropsychologist was available. Both a valid baseline and Visit 5 (week 24) assessment had to be present.

This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (\>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (\<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=29 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Old)
Worsened
1 Number of subjects
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Old)
Stable
20 Number of subjects
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Old)
Improved
8 Number of subjects

SECONDARY outcome

Timeframe: Visit 7 (week 48)

Population: The Bayley Scale of Infant Development (BSID) II assessment was performed only at selected sites where a neuropsychologist was available. Both a valid baseline and Visit 7 (week 48) assessment had to be present.

This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (\>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (\<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=24 Participants
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Old)
Worsened
1 Number of subjects
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Old)
Stable
15 Number of subjects
Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Old)
Improved
8 Number of subjects

Adverse Events

Levetiracetam

Serious events: 46 serious events
Other events: 206 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Levetiracetam
n=255 participants at risk
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Blood and lymphatic system disorders
Neutropenia
0.39%
1/255 • Number of events 1 • Up to 1 year
Blood and lymphatic system disorders
Thrombocytopenia
0.39%
1/255 • Number of events 1 • Up to 1 year
Congenital, familial and genetic disorders
Hip dysplasia
0.39%
1/255 • Number of events 1 • Up to 1 year
Gastrointestinal disorders
Abdominal pain
0.39%
1/255 • Number of events 1 • Up to 1 year
Gastrointestinal disorders
Constipation
0.39%
1/255 • Number of events 1 • Up to 1 year
Gastrointestinal disorders
Gastrooesophageal reflux disease
0.39%
1/255 • Number of events 1 • Up to 1 year
Gastrointestinal disorders
Small intestinal obstruction
0.39%
1/255 • Number of events 1 • Up to 1 year
General disorders
Influenza like illness
0.39%
1/255 • Number of events 1 • Up to 1 year
General disorders
Pyrexia
1.6%
4/255 • Number of events 4 • Up to 1 year
Investigations
Hepatic enzyme increased
0.39%
1/255 • Number of events 1 • Up to 1 year
Investigations
Transaminases increased
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Bacteraemia
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Bronchitis
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Exanthema subitum
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Gastroenteritis
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Gastroenteritis adenovirus
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Influenza
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Nasopharyngitis
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Pneumonia
2.4%
6/255 • Number of events 7 • Up to 1 year
Infections and infestations
Respiratory tract infection viral
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Septic shock
0.39%
1/255 • Number of events 1 • Up to 1 year
Infections and infestations
Upper respiratory tract infection
0.78%
2/255 • Number of events 3 • Up to 1 year
Infections and infestations
Viral infection
2.0%
5/255 • Number of events 5 • Up to 1 year
Injury, poisoning and procedural complications
Drug toxicity
0.39%
1/255 • Number of events 1 • Up to 1 year
Injury, poisoning and procedural complications
Feeding tube complication
0.39%
1/255 • Number of events 1 • Up to 1 year
Injury, poisoning and procedural complications
Head injury
0.78%
2/255 • Number of events 2 • Up to 1 year
Injury, poisoning and procedural complications
Pneumothorax traumatic
0.39%
1/255 • Number of events 1 • Up to 1 year
Metabolism and nutrition disorders
Feeding disorder of infancy or early childhood
0.39%
1/255 • Number of events 1 • Up to 1 year
Nervous system disorders
Brain oedema
0.78%
2/255 • Number of events 2 • Up to 1 year
Nervous system disorders
Convulsion
7.1%
18/255 • Number of events 22 • Up to 1 year
Nervous system disorders
Infantile spasms
0.39%
1/255 • Number of events 1 • Up to 1 year
Nervous system disorders
Partial seizures with secondary generalisation
0.39%
1/255 • Number of events 1 • Up to 1 year
Nervous system disorders
Status epilepticus
2.4%
6/255 • Number of events 14 • Up to 1 year
Psychiatric disorders
Crying
0.39%
1/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Aspiration
0.78%
2/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Choking
0.39%
1/255 • Number of events 1 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Hypoxia
0.39%
1/255 • Number of events 1 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
0.78%
2/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
0.78%
2/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
0.78%
2/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.78%
2/255 • Number of events 2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
0.39%
1/255 • Number of events 1 • Up to 1 year
Skin and subcutaneous tissue disorders
Rash
0.39%
1/255 • Number of events 1 • Up to 1 year
Surgical and medical procedures
Oesophagogastric fundoplasty
0.39%
1/255 • Number of events 1 • Up to 1 year

Other adverse events

Other adverse events
Measure
Levetiracetam
n=255 participants at risk
Oral tablets or oral solution at 10 to 30 mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.
Gastrointestinal disorders
Constipation
7.1%
18/255 • Number of events 24 • Up to 1 year
Gastrointestinal disorders
Diarrhoea
13.3%
34/255 • Number of events 45 • Up to 1 year
Gastrointestinal disorders
Vomiting
16.1%
41/255 • Number of events 62 • Up to 1 year
General disorders
Irritability
10.6%
27/255 • Number of events 33 • Up to 1 year
General disorders
Pyrexia
31.8%
81/255 • Number of events 131 • Up to 1 year
Infections and infestations
Bronchitis
6.3%
16/255 • Number of events 22 • Up to 1 year
Infections and infestations
Ear infection
7.1%
18/255 • Number of events 29 • Up to 1 year
Infections and infestations
Influenza
6.3%
16/255 • Number of events 22 • Up to 1 year
Infections and infestations
Nasopharyngitis
14.9%
38/255 • Number of events 53 • Up to 1 year
Infections and infestations
Otitis media
8.2%
21/255 • Number of events 34 • Up to 1 year
Infections and infestations
Pharyngitis
5.9%
15/255 • Number of events 30 • Up to 1 year
Infections and infestations
Rhinitis
5.5%
14/255 • Number of events 20 • Up to 1 year
Infections and infestations
Upper respiratory tract infection
24.3%
62/255 • Number of events 105 • Up to 1 year
Nervous system disorders
Somnolence
7.8%
20/255 • Number of events 24 • Up to 1 year
Metabolism and nutrition disorders
Decreased appetite
5.5%
14/255 • Number of events 17 • Up to 1 year
Nervous system disorders
Convulsion
6.7%
17/255 • Number of events 20 • Up to 1 year
Nervous system disorders
Headache
12.2%
31/255 • Number of events 46 • Up to 1 year
Psychiatric disorders
Aggression
5.9%
15/255 • Number of events 17 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Cough
11.4%
29/255 • Number of events 39 • Up to 1 year
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
5.5%
14/255 • Number of events 20 • Up to 1 year
Skin and subcutaneous tissue disorders
Rash
9.4%
24/255 • Number of events 28 • Up to 1 year

Additional Information

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