Trial Outcomes & Findings for Clinical Study of Lamotrigine to Treat Newly Diagnosed Typical Absence Seizure in Children and Adolescents (NCT NCT01431976)

NCT ID: NCT01431976

Last Updated: 2017-03-08

Results Overview

EEG is a diagnostic test for epilepsy. The EEG machine records the brain's electrical activity as a series of waveforms. HV is an activation technique used to provoke seizures during an EEG recording. An approximately 30-minute EEG with HV was performed on participants in a supine position. In the HV test, participants breathed through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes using a pin-wheel provided to them.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

20 participants

Primary outcome timeframe

Week 12 of the Maintenance Phase (up to Study Week 50)

Results posted on

2017-03-08

Participant Flow

Participants with newly diagnosed and untreated typical absence seizure; aged 2-15 years in Japan, 2-12 years in South Korea at the time of obtaining consent; weighing at least 7 kilograms (kg); without partial seizure or generalized seizures other than typical absence; and without a history of rash associated with other treatment were enrolled.

The study consisted of an Escalation Phase (EP), a 12-week (W) Maintenance Phase (MP), a \>=2-week Taper Phase, and post-study examination within 1-4 weeks after the last dose of lamotrigine. Participants could have entered the Extension Phase (ExP) until approval for this indication or until 24 months after the Last Subject Last Visit in the MP.

Participant milestones

Participant milestones
Measure	Lamotrigine In the EP, lamotrigine 0.3 milligrams per kilogram per day (mg/kg/day) was administered orally once daily from Week W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, whichever was less (WWL), until a seizure-free (SF) status was confirmed by hyperventilation (HV)-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Overall Study STARTED	20
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Lamotrigine In the EP, lamotrigine 0.3 milligrams per kilogram per day (mg/kg/day) was administered orally once daily from Week W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, whichever was less (WWL), until a seizure-free (SF) status was confirmed by hyperventilation (HV)-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Overall Study Adverse Event	6
Overall Study Lack of Efficacy	2
Overall Study Met Protocol-defined Stopping Criteria	4
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Clinical Study of Lamotrigine to Treat Newly Diagnosed Typical Absence Seizure in Children and Adolescents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Age, Continuous	7.7 Years STANDARD_DEVIATION 1.95 • n=99 Participants
Sex: Female, Male Female	13 Participants n=99 Participants
Sex: Female, Male Male	7 Participants n=99 Participants
Race/Ethnicity, Customized East Asian Heritage	3 participants n=99 Participants
Race/Ethnicity, Customized Japanese Heritage	16 participants n=99 Participants
Race/Ethnicity, Customized South East Asian Heritage	1 participants n=99 Participants

PRIMARY outcome

Timeframe: Week 12 of the Maintenance Phase (up to Study Week 50)

Population: Full Analysis Set (FAS): all participants who took at least one dose of investigational product and contributed data to at least one efficacy measure after the first dosing of investigational product

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by Hyperventilation (HV)-Electroencephalography (EEG) at the End of the Maintenance Phase (MP)	7 Participants

SECONDARY outcome

Timeframe: Up to Study Week 49

Population: FAS

EEG is a diagnostic test for epilepsy. The EEG machine records the brain's electrical activity as a series of waveforms. HV is an activation technique used to provoke seizures during an EEG recording. An approximately 30-minute EEG with HV was performed on participants in a supine position. In the HV test, participants breathed through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute ) for 4 continuous minutes using a pin-wheel provided to them.

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Two Consecutive Visits in the Escalation Phase (EP)	8 Participants

SECONDARY outcome

Timeframe: Up to Study Week 49

Population: FAS. Only those participants given the indicated dose of investigational product were analyzed.

HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the Escalation Phase, HV-clinical signs were assessed to confirm a status of seizure free. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 0.6 mg/kg, n=17	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 1.2 mg/kg, n=17	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 1.8 mg/kg, n=16	2 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 2.4 mg/kg, n=16	2 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 3.0 mg/kg, n=16	2 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 3.6 mg/kg, n=15	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 4.2 mg/kg, n=15	0 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 4.8 mg/kg, n=14	4 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 5.4 mg/kg, n=14	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 6.0 mg/kg, n=11	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 6.6 mg/kg, n=11	0 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 7.2 mg/kg, n=9	3 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 7.8 mg/kg, n=9	0 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 8.4 mg/kg, n=6	2 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 9.0 mg/kg, n=6	1 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase 9.6 mg/kg, n=1	1 Participants

SECONDARY outcome

Timeframe: Week 4 and Week 8 of the Maintenance Phase (up to Study Weeks 42 and 46, respectively)

Population: FAS. Only those participants who were dosed with investigational product at the indicated time points were analyzed.

HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the Maintenace Phase, HV-clinical signs were assessed at Visit 1 (Week 4) and Visit 2 (Week 4).

Outcome measures

Outcome measures
Measure	Lamotrigine n=7 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs During Week 4 and Week 8 of the Maintenance Phase Week 4	7 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs During Week 4 and Week 8 of the Maintenance Phase Week 8	7 Participants

SECONDARY outcome

Timeframe: Extension Week 12 (Extension Visit 1 [Ext-V1]), every 24 weeks after Ext-V1 and until withdrawal

Population: FAS. Only those participants given the indicated dose of investigational product were analyzed.

EEG is a diagnostic test for epilepsy. The EEG machine records the brain's electrical activity as a series of waveforms. HV is an activation technique used to provoke seizures during an EEG recording. An approximately 30-minute EEG with HV was performed on participants in a supine position. In the HV test, participants breathed through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute ) for 4 continuous minutes using a pin-wheel provided to them. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 12, n=7	6 Participants 1.568
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 36, n=7	5 Participants 2.114
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 60, n=7	6 Participants 0.161
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 84, n=6	6 Participants 2.197
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 108, n=6	6 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 132, n=6	6 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) Extension Week 156, n=2	2 Participants

SECONDARY outcome

Timeframe: Extension Week 24 (Extension Visit 2 [Ext-V2], every 24 weeks after the Ext-V2 and until withdrawal

Population: FAS. Only those participants given the indicated dose of investigational product were analyzed.

HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the ExP, HV-clinical signs were assessed to confirm a status of seizure free. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 24, n=7	5 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 48, n=7	6 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 72, n=7	5 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 96, n=6	6 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 120, n=6	5 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 144, n=4	2 Participants
Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) Extension Week 168, n=1	1 Participants

SECONDARY outcome

Timeframe: Up to Study Week 50

Population: FAS

Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title)

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Days With Seizure Episodes Per Week in the Main Study Phase (Fixed Escalation Phase [FEP], Escalation Phase [EP], Maintenance Phase [MP]), and FEP+EP+MP) Fixed Escalation Phase, n=20	4.93 Days Standard Deviation 1.488
Number of Days With Seizure Episodes Per Week in the Main Study Phase (Fixed Escalation Phase [FEP], Escalation Phase [EP], Maintenance Phase [MP]), and FEP+EP+MP) Escalation Phase, n=17	2.60 Days Standard Deviation 2.060
Number of Days With Seizure Episodes Per Week in the Main Study Phase (Fixed Escalation Phase [FEP], Escalation Phase [EP], Maintenance Phase [MP]), and FEP+EP+MP) Maintenance Phase, n=8	0.06 Days Standard Deviation 0.161
Number of Days With Seizure Episodes Per Week in the Main Study Phase (Fixed Escalation Phase [FEP], Escalation Phase [EP], Maintenance Phase [MP]), and FEP+EP+MP) FEP+EP+MP, n=20	2.98 Days Standard Deviation 1.976

SECONDARY outcome

Timeframe: Extension Week 12 (Extension Visit 1 [Ext-V1], every 12 week after Ext-V1 and until withdrawal

Population: FAS. Only those participants given the indicated dose of investigational product were analyzed.

Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided.

Outcome measures

Outcome measures
Measure	Lamotrigine n=7 Participants In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Number of Days With Seizure Episodes Per Week in the Extension Phase (ExP) Overall	0.03 Days Standard Deviation 0.048

Adverse Events

Lamotrigine

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lamotrigine n=20 participants at risk In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at \>=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose \<1.2 mg/kg/day or \>10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study.
Infections and infestations Bronchitis	25.0% 5/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Nasopharyngitis	35.0% 7/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Upper respiratory tract infection	15.0% 3/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Cellulitis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Gastroenteritis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Influenza	25.0% 5/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Paronychia	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Pharyngitis	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Pneumonia mycoplasmal	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Scarlet fever	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Varicella	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Adenovirus infection	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Folliculitis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Otitis media acute	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Rhinitis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Sinusitis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Infections and infestations Conjunctivitis	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Rash	30.0% 6/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Drug eruption	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Dermatitis atopic	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Eczema	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Acne	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Dry skin	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Skin and subcutaneous tissue disorders Urticaria	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Fracture	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Arthropod bite	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Arthropod sting	15.0% 3/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Chillblains	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Skin abrasion	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Injury, poisoning and procedural complications Hand fracture	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Nervous system disorders Headache	20.0% 4/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Nervous system disorders Psychomotor hyperactivity	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Nervous system disorders Febrile convulsion	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Stomatitis	10.0% 2/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Constipation	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Enteritis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Gastrointestinal disorders Enterocolitis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Immune system disorders Drug hypersensitivity	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Immune system disorders Seasonal allergy	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Metabolism and nutrition disorders Decreased appetite	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Metabolism and nutrition disorders Dehydration	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Investigations Alanine aminotransferase increased	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Investigations Aspartate aminotransferase increased	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Renal and urinary disorders Proteinuria	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Renal and urinary disorders Hematuria	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
General disorders Pain	5.0% 1/20 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

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