An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures

• ClinicalTrials.gov Identifier: NCT01063764
• Recruitment Status: Completed
• First Posted: February 5, 2010
• Results First Posted: June 19, 2012
• Last Update Posted: March 5, 2015
• Sponsor: UCB Japan Co. Ltd.
• Information provided by (Responsible Party): UCB Pharma ( UCB Japan Co. Ltd. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Epilepsy; Partial Seizures
• Intervention: Drug: Levetiracetam
• Enrollment: 73

Participant Flow

Recruitment Details	Full Analysis Set (FAS) includes all subjects taking at least one dose of study medication. Per-Protocol Set (PPS) is a subset of the FAS, consisting of subjects without major protocol violations affecting the primary efficacy variable.
Pre-assignment Details	Participant Flow refers to the Full Analysis Set. First Period started after Baseline (Week 0 to Week 8).

Arm/Group Title	Levetiracetam
Arm/Group Description	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Period Title: 1st Period (From Week 8 to Week 22)
Started	73
Completed	62 [1]
Not Completed	11
Reason Not Completed
Adverse Event	4
Lack of Efficacy	6
Withdrawal by Subject	1
[1] 62 subjects completed the First Period, but 7 of these subjects did not enter the Second Period.
Period Title: 2nd Period (Week 22 to the End of Study)
Started	55 [1]
Completed	35
Not Completed	20
Reason Not Completed
Adverse Event	3
Lack of Efficacy	9
Withdrawal by Subject	7
Protocol Violation	1
[1] 7 subjects who completed Period 1 did not enter the Second Period.

Baseline Characteristics

Arm/Group Title		Levetiracetam
Arm/Group Description		First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Baseline Participants		73
Baseline Analysis Population Description		Baseline Characteristics refer to the Full Analysis Set (FAS). FAS includes all subjects taking at least one dose of study medication.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	73 participants
		10.1 (3.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	73 participants
	Female	32 43.8%
	Male	41 56.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Japan	Number Analyzed	73 participants
		73
Age Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants
>=4 - <8 years		22
>=8 - <12 years		22
>=12 - <16 years		29
Body Weight; Mean (Standard Deviation); Unit of measure: Kilogram (kg)
	Number Analyzed	73 participants
		32.43 (13.20)
Height; Mean (Standard Deviation); Unit of measure: Centimeter (cm)
	Number Analyzed	73 participants
		134.55 (20.69)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kilogram / meter^2 (kg/m^2)
	Number Analyzed	73 participants
		17.15 (2.99)
Hospitalization Status; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants
Yes		0
No		73

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
Description	The change in partial seizure frequency from Baseline (B) over the Treatment Period (T) is given as a percentage reduction computed as: (B values- T values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline during the first 14-week Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)); Week 0-22

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	73
Median (95% Confidence Interval); Unit of Measure: Percent reduction
	43.21; (26.19 to 52.14)

2. Primary Outcome

Title	Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Second Period (up to Three Years Until the Time of Approval Granted)
Description	An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with the pharmaceutical product. Incidence of treatment-emergent AEs is reported by the percentage of subjects with at least one treatment-emergent AE.
Time Frame	During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	55
Measure Type: Number; Unit of Measure: percentage of participants
	98.2

3. Secondary Outcome

Title	Change From Baseline in Partial Seizure Frequency Per Week Over the 10-week Evaluation Period
Description	The change in partial seizure frequency from Baseline (B) over the Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline to the 10-week Evaluation Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	From Baseline (Week 0-8) to the 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)

Outcome Measure Data

Analysis Population Description

Of the 73 subjects in the FAS, 68 subjects had available data at Baseline and during the Evaluation Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	68
Median (95% Confidence Interval); Unit of Measure: Percent reduction
	39.02; (26.67 to 52.07)

4. Secondary Outcome

Title	Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
Description	The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Treatment Period/number of days for observation in the Treatment Period) x 7. Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Only subjects having values unequal to zero over Baseline and values equal to or greater than zero over Treatment Period are included.

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	73
Median (Inter-Quartile Range); Unit of Measure: Seizures per week
	3.92; (0.93 to 17.08)

5. Secondary Outcome

Title	Partial Seizure Frequency Per Week Over the 10-weeks Evaluation Period
Description	The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Evaluation Period/number of days for observation in the Evaluation Period) x 7. Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Only subjects having values unequal to zero over Baseline and values equal to or greater than zero over Treatment Period are included.

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	68
Median (Inter-Quartile Range); Unit of Measure: Seizures per week
	3.90; (0.86 to 17.26)

6. Secondary Outcome

Title	Percentage of Partial Seizures 50 % Responders Over the 14-weeks Treatment Period
Description	50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Treatment Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	73
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	38.4; (27.2 to 50.5)

7. Secondary Outcome

Title	Percentage of Partial Seizures 50 % Responders Over the 10-weeks Evaluation Period
Description	50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Evaluation Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)

Outcome Measure Data

Analysis Population Description

Of the 73 subjects in the FAS, 68 subjects had available data over the Evaluation Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	68
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	38.2; (26.7 to 50.8)

8. Secondary Outcome

Title	Number of Seizure-free Subjects Over the 14-weeks Treatment Period
Description	Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	73
Measure Type: Number; Unit of Measure: participants
	2

9. Secondary Outcome

Title	Number of Seizure-free Subjects Over the 10-weeks Evaluation Period
Description	Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: Simple partial seizures; Complex partial seizures; Partial seizures evolving to secondarily generalized seizures.
Time Frame	10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)

Outcome Measure Data

Analysis Population Description

Of the 73 subjects in the FAS, 68 subjects had available data over the Evaluation Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	68
Measure Type: Number; Unit of Measure: participants
	3

10. Secondary Outcome

Title	Incidence of Treatment-emergent Adverse Drug Reactions (ADRs) During the Second Period (up to Three Years Until the Time of Approval Granted)
Description	An Adverse Drug Reaction (ADR) is an Adverse Event for which a causal relationship between the product and the occurrence is suspected. Incidence of ADRs is reported by the number of subjects with at least one ADR.
Time Frame	During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	55
Measure Type: Number; Unit of Measure: participants
	15

11. Secondary Outcome

Title	Change From Baseline in Partial Seizure Frequency Per Week for the Second Period (up to Three Years From Informed Consent Until the Time of Approval Granted)
Description	The outcome was also calculated for each 3-month Period but here only the result for the total Second Evaluation Period (Second Period without following 6-weeks Withdrawal Period for withdrawers) is presented. Change in partial seizure frequency from Baseline (B) over Second Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction show a decrease from Baseline. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7.
Time Frame	From Baseline (Week 0-8) until the time of approval granted (up to three years from date of informed consent (Week 0); without 6-weeks Withdrawal Period)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
Overall Number of Participants Analyzed	55
Median (Inter-Quartile Range); Unit of Measure: Percent reduction
	41.32; (15.37 to 82.40)

Adverse Events

Time Frame	Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
Adverse Event Reporting Description	AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
Arm/Group Title	Levetiracetam
Arm/Group Description	First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.; Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
All-Cause Mortality
	Levetiracetam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	8/73 (10.96%)
Eye disorders
Strabismus * 1	1/73 (1.37%)	1
Gastrointestinal disorders
Abdominal pain lower * 1	1/73 (1.37%)	1
Acetonaemic vomiting * 1	1/73 (1.37%)	2
Dental caries * 1	1/73 (1.37%)	1
Infections and infestations
Gastroenteritis * 1	2/73 (2.74%)	2
Pneumonia * 1	1/73 (1.37%)	1
Injury, poisoning and procedural complications
Near drowning * 1	1/73 (1.37%)	1
Nervous system disorders
Convulsion * 1	2/73 (2.74%)	2
Status epilepticus * 1	1/73 (1.37%)	1
Psychiatric disorders
Conversion disorder * 1	1/73 (1.37%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (14.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	66/73 (90.41%)
Eye disorders
Conjunctivitis * 1	4/73 (5.48%)	5
Gastrointestinal disorders
Diarrhoea * 1	9/73 (12.33%)	16
Nausea * 1	5/73 (6.85%)	5
Abdominal Pain * 1	5/73 (6.85%)	7
Constipation * 1	6/73 (8.22%)	7
Dental Caries * 1	5/73 (6.85%)	11
General disorders
Pyrexia * 1	17/73 (23.29%)	32
Irritability * 1	4/73 (5.48%)	4
Infections and infestations
Nasopharyngitis * 1	54/73 (73.97%)	205
Influenza * 1	20/73 (27.40%)	24
Upper respiratory tract infection * 1	12/73 (16.44%)	37
Gastroenteritis * 1	7/73 (9.59%)	13
Impetigo * 1	4/73 (5.48%)	4
Pharyngitis * 1	4/73 (5.48%)	4
Injury, poisoning and procedural complications
Contusion * 1	8/73 (10.96%)	11
Excoriation * 1	6/73 (8.22%)	8
Wound * 1	5/73 (6.85%)	10
Arthropod bite * 1	4/73 (5.48%)	21
Metabolism and nutrition disorders
Decreased appetite * 1	5/73 (6.85%)	5
Nervous system disorders
Somnolence * 1	34/73 (46.58%)	48
Headache * 1	10/73 (13.70%)	20
Convulsion * 1	7/73 (9.59%)	8
Psychiatric disorders
Agitation * 1	4/73 (5.48%)	4
Respiratory, thoracic and mediastinal disorders
Epistaxis * 1	6/73 (8.22%)	8
Rhinorrhoea * 1	5/73 (6.85%)	10
Cough * 1	4/73 (5.48%)	5
Rhinitis allergic * 1	4/73 (5.48%)	4
Skin and subcutaneous tissue disorders
Acne * 1	6/73 (8.22%)	6
Heat rash * 1	5/73 (6.85%)	5
Eczema * 1	4/73 (5.48%)	5
Pruritus * 1	4/73 (5.48%)	6
Rash * 1	4/73 (5.48%)	6
Urticaria * 1	4/73 (5.48%)	4
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (14.0)

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493 (UCB)

Publications of Results:

Nakamura H, Osawa M, Yokoyama T, Yoshida K, Suzuki A. [Efficacy and safety of levetiracetam as adjunctive therapy in Japanese children with uncontrolled partial-onset seizures: multicenter and open-label study (N01223), short term evaluation]. Brain Nerve. 2013 Sep;65(9):1083-92. Japanese.

• Responsible Party: UCB Pharma ( UCB Japan Co. Ltd. )
• ClinicalTrials.gov Identifier: NCT01063764
• Other Study ID Numbers: N01223; 2014-004335-39 ( EudraCT Number )
• First Submitted: February 1, 2010
• First Posted: February 5, 2010
• Results First Submitted: March 28, 2012
• Results First Posted: June 19, 2012
• Last Update Posted: March 5, 2015