Trial Outcomes & Findings for A Study of Levetiracetam in Japanese Pediatric Patients With Generalized Tonic-clonic Seizures (NCT NCT01292837)

Last Updated: 2015-05-15

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

13 participants

Primary outcome timeframe

From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)

Results posted on

2015-05-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Levetiracetam 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 Study STARTED	13
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Levetiracetam 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 Study Adverse Event	1
Overall Study Further treatment determined	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Levetiracetam n=13 Participants 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.
Age, Continuous	9.7 years STANDARD_DEVIATION 4.1 • n=5 Participants
Age, Customized ≥4 to <8 years	4 participants n=5 Participants
Age, Customized ≥8 to <12 years	2 participants n=5 Participants
Age, Customized ≥12 to <16 years	7 participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Region of Enrollment Japan	13 participants n=5 Participants
Weight	32.22 kilogram STANDARD_DEVIATION 16.56 • n=5 Participants
Height	129.36 centimeter STANDARD_DEVIATION 26.32 • n=5 Participants
Body Mass Index	17.89 kilogram per squaremeter (kg/m^2) STANDARD_DEVIATION 3.75 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)

Population: 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.

Outcome measures

Outcome measures
Measure	Levetiracetam n=13 Participants 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.
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)	45.47 percent change Standard Deviation 50.34

SECONDARY outcome

Timeframe: From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Levetiracetam n=12 Participants 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.
The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period	44.93 percent change Standard Deviation 51.86

SECONDARY outcome

Timeframe: From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)

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.

Outcome measures

Outcome measures
Measure	Levetiracetam n=13 Participants 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.
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	53.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)

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.

Outcome measures

Outcome measures
Measure	Levetiracetam n=12 Participants 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.
Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period	58.3 percentage of participants

SECONDARY outcome

Timeframe: Treatment Period (Week 0 to Week 24)

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.

Outcome measures

Outcome measures
Measure	Levetiracetam n=13 Participants 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.
Generalized Tonic-clonic Seizure Freedom Over the Treatment Period	2 participants

SECONDARY outcome

Timeframe: Evaluation Period (Week 4 to Week 24)

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.

Outcome measures

Outcome measures
Measure	Levetiracetam n=12 Participants 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.
Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period	2 participants

Adverse Events

Levetiracetam

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Levetiracetam n=13 participants at risk 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.
Gastrointestinal disorders Diarrhoea	15.4% 2/13 • Number of events 5 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Infections and infestations Nasopharyngitis	23.1% 3/13 • Number of events 5 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Nervous system disorders Convulsion	23.1% 3/13 • Number of events 5 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Nervous system disorders Somnolence	23.1% 3/13 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Gastrointestinal disorders Dental caries	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Gastrointestinal disorders Stomatitis	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
General disorders Pyrexia	7.7% 1/13 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Infections and infestations Impetigo	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Infections and infestations Otitis media	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Infections and infestations Pneumonia mycoplasmal	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Injury, poisoning and procedural complications Arthropod sting	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Injury, poisoning and procedural complications Contusion	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Injury, poisoning and procedural complications Laceration	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Injury, poisoning and procedural complications Subcutaneous haematoma	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Investigations Electrocardiogram QT prolonged	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Metabolism and nutrition disorders Decreased appetite	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Nervous system disorders Bradykinesia	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Respiratory, thoracic and mediastinal disorders Respiratory tract haemorrhage	7.7% 1/13 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Skin and subcutaneous tissue disorders Dermatitis	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Skin and subcutaneous tissue disorders Excessive granulation tissue	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to Week 30 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.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: ++1 877 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60