A Study of Levetiracetam in Japanese Pediatric Patients With Generalized Tonic-clonic Seizures

• ClinicalTrials.gov Identifier: NCT01292837
• Recruitment Status: Completed
• First Posted: February 10, 2011
• Results First Posted: August 12, 2014
• Last Update Posted: May 15, 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; Generalized Tonic-clonic Seizures
• Intervention: Drug: Levetiracetam
• Enrollment: 13

Participant Flow

Recruitment Details	This multicenter study started to enroll subjects in Februray 2011 in order to end up with 8 sites in Japan with enrolled subjects. Participant Flow refers to the Enrolled Set (ES). ES consists of all subjects who signed the consent form and participated in the Prospective Baseline Period.
Pre-assignment Details

Arm/Group Title	Levetiracetam
Arm/Group Description	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Period Title: Overall Study
Started	13
Completed	11
Not Completed	2
Reason Not Completed
Adverse Event	1
Further treatment determined	1

Baseline Characteristics

Arm/Group Title		Levetiracetam
Arm/Group Description		Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Baseline Participants		13
Baseline Analysis Population Description		The Baseline Analysis Population refers to the Safety Set. The Safety Set was a subset of the Enrolled Set and consisted of all subjects taking at least 1 dose of the study medication.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	13 participants
		9.7 (4.1)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	13 participants
≥4 to <8 years		4
≥8 to <12 years		2
≥12 to <16 years		7
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants
	Female	4 30.8%
	Male	9 69.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Japan	Number Analyzed	13 participants
		13
Weight; Mean (Standard Deviation); Unit of measure: Kilogram
	Number Analyzed	13 participants
		32.22 (16.56)
Height; Mean (Standard Deviation); Unit of measure: Centimeter
	Number Analyzed	13 participants
		129.36 (26.32)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kilogram per squaremeter (kg/m^2)
	Number Analyzed	13 participants
		17.89 (3.75)

Outcome Measures

1. Primary Outcome

Title	The Percent Change From the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 24-week Treatment Period (Up-Titration and Evaluation Periods)
Description	The percent change from Combined Baseline over Treatment Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Treatment Period (T) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - T)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
Time Frame	From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: percent change
	45.47 (50.34)

2. Secondary Outcome

Title	The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period
Description	The percent change from Combined Baseline over Evaluation Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Evaluation Period (E) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - E)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
Time Frame	From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with combined Baseline Period and post-Baseline generalized tonic-clonic seizure counts. 12 of the 13 subjects in the FAS were included in the analysis excluding 1 subject discontinued before the Evaluation Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: percent change
	44.93 (51.86)

3. Secondary Outcome

Title	Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period
Description	The 50 % responder rate during the Treatment Period was the proportion of subjects who reported a ≥ 50 % reduction in seizure frequency per week from Baseline during the Treatment Period.
Time Frame	From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Unit of Measure: percentage of participants
	53.8

4. Secondary Outcome

Title	Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period
Description	The 50 % responder rate during the Evaluation Period was the proportion of subjects who reported a ≥50 % reduction in seizure frequency per week from Baseline during the Evaluation Period.
Time Frame	From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.

One subject discontinued the study during the Up-Titration Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: percentage of participants
	58.3

5. Secondary Outcome

Title	Generalized Tonic-clonic Seizure Freedom Over the Treatment Period
Description	A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Treatment Period was considered a seizure-free subject for that period.
Time Frame	Treatment Period (Week 0 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Unit of Measure: participants
	2

6. Secondary Outcome

Title	Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period
Description	A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Evaluation Period was considered a seizure-free subject for that period.
Time Frame	Evaluation Period (Week 4 to Week 24)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS was a subset of the Safety Set and included all subjects with Combined Baseline Period (Retrospective and Prospective) and post-Baseline Generalized Tonic-Clonic seizure counts as the primary efficacy analysis.

One subject discontinued the study during the Up-Titration Period.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: participants
	2

Adverse Events

Time Frame	Treatment Emergent Adverse Events were reported from Baseline up to Week 30
Adverse Event Reporting Description	The Analysis Population refers to the Safety Set. The Safety Set was a subset of the Enrolled Set and consisted of all subjects taking at least 1 dose of the study medication.
Arm/Group Title	Levetiracetam
Arm/Group Description	Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
All-Cause Mortality
	Levetiracetam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	0/13 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	13/13 (100.00%)
Gastrointestinal disorders
Diarrhoea * 1	2/13 (15.38%)	5
Dental caries * 1	1/13 (7.69%)	1
Stomatitis * 1	1/13 (7.69%)	1
General disorders
Pyrexia * 1	1/13 (7.69%)	2
Infections and infestations
Nasopharyngitis * 1	3/13 (23.08%)	5
Impetigo * 1	1/13 (7.69%)	1
Otitis media * 1	1/13 (7.69%)	1
Pneumonia mycoplasmal * 1	1/13 (7.69%)	1
Injury, poisoning and procedural complications
Arthropod sting * 1	1/13 (7.69%)	1
Contusion * 1	1/13 (7.69%)	1
Laceration * 1	1/13 (7.69%)	1
Subcutaneous haematoma * 1	1/13 (7.69%)	1
Investigations
Electrocardiogram QT prolonged * 1	1/13 (7.69%)	1
Metabolism and nutrition disorders
Decreased appetite * 1	1/13 (7.69%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity * 1	1/13 (7.69%)	1
Nervous system disorders
Convulsion * 1	3/13 (23.08%)	5
Somnolence * 1	3/13 (23.08%)	3
Bradykinesia * 1	1/13 (7.69%)	1
Headache * 1	1/13 (7.69%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis * 1	1/13 (7.69%)	1
Respiratory tract haemorrhage * 1	1/13 (7.69%)	2
Rhinitis allergic * 1	1/13 (7.69%)	1
Skin and subcutaneous tissue disorders
Dermatitis * 1	1/13 (7.69%)	1
Excessive granulation tissue * 1	1/13 (7.69%)	1
Rash * 1	1/13 (7.69%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0

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

• Responsible Party: UCB Pharma ( UCB Japan Co. Ltd. )
• ClinicalTrials.gov Identifier: NCT01292837
• Other Study ID Numbers: N01363; 2014-004382-25 ( EudraCT Number )
• First Submitted: February 8, 2011
• First Posted: February 10, 2011
• Results First Submitted: June 3, 2014
• Results First Posted: August 12, 2014
• Last Update Posted: May 15, 2015