Preventing Epilepsy Using Vigabatrin In Infants With Tube... | NCT02849457

ID	Type	Description	Link
1U01NS092595-01A1	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Institute of Neurological Disorders and Stroke (NINDS)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Delayed Vigabatrin (Placebo)	Placebo Comparator	Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.	Drug: Early Vigabatrin Drug: Delayed Vigabatrin (Placebo)
Early Vigabatrin	Experimental	Randomization will only occur after detection of epileptiform activity on EEG. Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.	Drug: Early Vigabatrin
Watchful Waiting (Control Group)	No Intervention	Enrolled participants in this arm are those who never develop EEG abnormalities or clinical seizures during the length of the study. While all participants who enrolled in the study started in this group, participants were randomized upon development of EEG epileptiform activity. All participants who completed the study without developing EEG epileptiform activity or clinical seizures are reported in this group.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Early Vigabatrin	Drug	Subjects randomized to vigabatrin will be treated with vigabatrin 100mg/kg/day until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on study drug, they will transition into the Open label phase of the study and continue to be followed until 36 months of age.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cognitive Assessment Scores and Developmental Impact	The primary outcome measure will be the standardized Cognitive scale scores on the Bayley Scales of Infant and Toddler Development- Third Edition at 24 months. The Cognitive scale Composite score is a standard score derived from the observed and elicited performance of the child on cognitive assessment tasks, with a mean of 100 and standard deviation of 10. The range for the Cognitive scale Composite score is 55 to 145. The score is calculated using standard procedures available in the manual for this measure. A higher score is considered better performance. The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and to compare the developmental impact of early versus delayed treatment with vigabatrin.	24 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.	Evaluate the number of subjects that develop seizures when treated with vigabatrin or placebo as a seizure prevention.	24 months
Time to the Subject's First Clinical Seizure From Randomization

Eligibility Module

Name	Affiliation	Role
Martina Bebin, MD, MPA	University of Alabama at Birmingham	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
University of California, Los Angeles

PubMed Identifier	Type	Citation	Retractions
37638552	Result	Bebin EM, Peters JM, Porter BE, McPherson TO, O'Kelley S, Sahin M, Taub KS, Rajaraman R, Randle SC, McClintock WM, Koenig MK, Frost MD, Northrup HA, Werner K, Nolan DA, Wong M, Krefting JL, Biasini F, Peri K, Cutter G, Krueger DA; PREVeNT Study Group. Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial. Ann Neurol. 2023 Aug 28:10.1002/ana.26778. doi: 10.1002/ana.26778. Online ahead of print.
31912454

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 2, 2020

Arm/Group Information

ID	Title	Description
BG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
BG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
BG002	Watchful Waiting (Control Group)	Enrolled participants in this arm are those who never develop EEG abnormalities or clinical seizures during the length of the study. While all participants who enrolled in the study started in this group, participants were randomized upon development of EEG epileptiform activity. All participants who completed the study without developing EEG epileptiform activity or clinical seizures are reported in this group.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cognitive Assessment Scores and Developmental Impact

The primary outcome measure will be the standardized Cognitive scale scores on the Bayley Scales of Infant and Toddler Development- Third Edition at 24 months. The Cognitive scale Composite score is a standard score derived from the observed and elicited performance of the child on cognitive assessment tasks, with a mean of 100 and standard deviation of 10. The range for the Cognitive scale Composite score is 55 to 145. The score is calculated using standard procedures available in the manual for this measure. A higher score is considered better performance. The Bayley Scales of Infant and Toddler Development at 24 months will be used for the data analysis and to compare the developmental impact of early versus delayed treatment with vigabatrin.

The analysis population was the intent to treat population. Three participants withdrew prior to 24 months of age, and one participant did not complete the Bayley assessment at 24 months.

Posted

Mean

Standard Deviation

score on a scale

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG002	Watchful Waiting (Control Group)	Enrolled participants in this arm are those who never develop EEG abnormalities or clinical seizures during the length of the study. While all participants who enrolled in the study started in this group, participants were randomized upon development of EEG epileptiform activity. All participants who completed the study without developing EEG epileptiform activity or clinical seizures are reported in this group.
OG003	Watchful Waiting (Open Label Vigabatrin)	Participants in this group experienced seizures prior to detection of EEG epileptiform activity and where immediately placed on open label Vigabatrin.

Units	Counts
Participants	OG00023 OG00129 OG00211 OG003

Title

Denominators

Categories

Title	Measurements
	OG00083.9± 17.3 OG00180.9± 15.6 OG00297.3± 16.9 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	Adjusted for age (<=7 vs >7 months) at randomization and sex. Unstructured covariance used among 12 and 24 month outcomes.	0.8681		Mean Difference (Final Values)	-0.6565	Standard Error of the Mean	3.9332	2-Sided	95	-8.5567	7.2436			Parameter represents estimated amount difference in group means. Negative value represents higher mean in placebo group.		Superiority

Secondary

Number of Subjects That Develop Seizures When Treated With Study Drug During the Randomized Phase of the Study.

Evaluate the number of subjects that develop seizures when treated with vigabatrin or placebo as a seizure prevention.

One participant in the Delayed Vigabatrin group withdrew prior to 24 months and prior to the development of any seizures. They were therefore excluded from count endpoints and from cognitive assessments at 24 months, although they were included in time to event analyses (censored at drop-out).

Posted

Count of Participants

Participants

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Secondary

Time to the Subject's First Clinical Seizure From Randomization

Time to the subject's first clinical seizure will be measured for both subjects on placebo and vigabatrin.

Posted

Median

95% Confidence Interval

Months from randomization

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Secondary

Count of Participants With Drug Resistant Epilepsy at 24 Months of Age.

The count of participants with drug resistant epilepsy. Drug resistant epilepsy classified according to International League Against Epilepsy (ILAE) definition, specifically defined as any participant on 2 or more anti-seizure medications experiencing persistent seizures (seizures occurring within 3 months of the 24 month participant visit).

Three participants in the Delayed Vigabatrin group withdrew prior to age 24 months and could therefore not be classified as has having drug resistant epilepsy or not at age 24 months.

Posted

Count of Participants

Participants

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin

Secondary

Evaluate Vineland II ABC Scores and Impact of Early Versus Late Treatment

The range for the Vineland-II Adaptive Behavior Composite is 20 to 160

The Vineland-II ABC standard score has a mean of 100 and standard deviation of 15, with higher scores indicating better overall adaptive functioning.

The ABC standard score is a composite derived from obtained scores on the Communication, Daily Living Skills, Socialization, and Motor Skills domains on the Vineland-II and is calculated according to standardized procedures described in the Vineland-II manual.

The analysis population was the intent to treat population. Three participants withdrew prior to 24 months of age, and 2 withdrew prior to 12 months of age.

Posted

Mean

Standard Deviation

score on a scale

12 months, 24 months and 36 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Secondary

Evaluate Autism Diagnostic Observation Schedule 2nd Edition (ADOS2) Scores and Impact of Early Versus Late Treatment

Evaluate ADOS2 scores and the impact of early versus late treatment at 24 and 36 months.

This outcome was not assessed because it required an in-person evaluation that could not be performed while wearing a face mask, which would have invalidated the assessment, and was thus eliminated as an outcome measure at the start of the COVID-19 pandemic.

Posted

24 months and 36 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Secondary

Number of Subjects With Vigabatrin Related Adverse Events and Severe Adverse Events

Number of subjects with vigabatrin related adverse events, severe adverse events as assessed by CTCAE v4.0 and risk evaluation and mitigation strategy (REMS) measures as required by the FDA.

Posted

Count of Participants

Participants

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Secondary

EEG Biomarker for Developing Epilepsy

Feasibility of the routine 1 hour video EEG in determining the EEG biomarker for developing epilepsy. Outcome was determined as the number of participants developing seizures amongst those developing the biomarker (epileptiform activity).

Posted

Count of Participants

Participants

24 months

ID	Title	Description
OG000	Delayed Vigabatrin (Placebo)	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.
OG001	Early Vigabatrin	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Delayed Vigabatrin (Placebo), Pre-randomization	Patients who were eventually randomized to the Delayed Vigabatrin (Placebo) arm. The adverse events reflected in this arm occurred prior to randomization and initiation of study drug.	27	3	27	4	27
EG001	Early Vigabatrin, Pre-randomization	Patients who were eventually randomized to the Early Vigabatrin arm. The adverse events reflected in this arm occurred prior to randomization and initiation of study drug.	29	2	29	4	29
EG002	Delayed Vigabatrin (Placebo), Post-randomization	Study drug (in this case, placebo) is given for administration, the entire content of one sachet (500 mg placebo) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with matching placebo until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on placebo, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.	27	14	27	15	27
EG003	Early Post-randomization	Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID). Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.	29	15	29	17	29
EG004	Watchful Waiting (Control Group)	Enrolled participants in this arm are those who never develop EEG abnormalities or clinical seizures during the length of the study. While all participants who enrolled in the study started in this group, participants were randomized upon development of EEG epileptiform activity. All participants who completed the study without developing EEG epileptiform activity or clinical seizures are reported in this group.	12	1	12	7	12
EG005	Watchful Waiting (Open Label Vigabatrin), Before Use of Vigabatrin	Participants in this group eventually had a seizure and were placed on open label vigabatrin; however, the adverse events in this arm occurred prior to beginning open label vigabatrin.	4	2	4	3	4
EG006	Watchful Waiting (Open Label Vigabatrin), After Starting Vigabatrin	Participants in this group experienced seizures prior to detection of EEG epileptiform activity and where immediately placed on open label Vigabatrin. The adverse events in this arm occurred after beginning open label vigabatrin.	4	2	4	3	4

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Infections and infestations	Infections and infestations	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0022 events2 affected27 at risk EG0031 events1 affected29 at risk EG0040 events0 affected12 at risk EG0050 events0 affected4 at risk EG0060 events0 affected4 at risk
Investigations	Investigations	Systematic Assessment	EG0000 events0 affected27 at risk EG0012 events1 affected29 at risk EG0020 events0 affected27 at risk EG003
Nervous system disorders	Nervous system disorders	Systematic Assessment	EG0002 events2 affected27 at risk EG0010 events0 affected29 at risk EG00230 events11 affected27 at risk EG003
Cardiac disorders	Cardiac disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected27 at risk EG003
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0023 events3 affected27 at risk EG003
Surgical and medical procedures	Surgical and medical procedures	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected27 at risk EG003
Congenital, familial and genetic disorders	Congenital, familial and genetic disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected27 at risk EG003
Eye disorders	Eye disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Immune system disorders	Immune system disorders	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0024 events3 affected27 at risk EG0033 events3 affected29 at risk EG0041 events1 affected12 at risk EG0050 events0 affected4 at risk EG0060 events0 affected4 at risk
Infections and infestations	Infections and infestations	Systematic Assessment	EG0000 events0 affected27 at risk EG0012 events2 affected29 at risk EG00230 events7 affected27 at risk EG003
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected27 at risk EG003
Investigations	Investigations	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003
Nervous system disorders	Nervous system disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003
Psychiatric disorders	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0021 events1 affected27 at risk EG003
Cardiac disorders	Cardiac disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0011 events1 affected29 at risk EG0020 events0 affected27 at risk EG003
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0025 events4 affected27 at risk EG003
Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events2 affected27 at risk EG0012 events2 affected29 at risk EG0026 events4 affected27 at risk EG003
Surgical and medical procedures	Surgical and medical procedures	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003
Ear and labyrinth disorders	Ear and labyrinth disorders	Systematic Assessment	EG0002 events1 affected27 at risk EG0010 events0 affected29 at risk EG0024 events3 affected27 at risk EG003
Eye disorders	Eye disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0023 events3 affected27 at risk EG003
Gastrointestinal disorders	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected27 at risk EG0010 events0 affected29 at risk EG0025 events3 affected27 at risk EG003
General disorders	General disorders	Systematic Assessment	EG0002 events2 affected27 at risk EG0010 events0 affected29 at risk EG0028 events3 affected27 at risk EG003
Blood and lymphatic system disorders	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003
Renal and urinary disorders	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected27 at risk EG0010 events0 affected29 at risk EG0020 events0 affected27 at risk EG003

Study drug (in this case, vigabatrin) is given for administration, the entire content of one sachet (500 mg vigabatrin) is dissolved in 10 ml water for oral administration that is dosed according to body weight 50-150 mg/kg/day divided BID. Dosing will follow established recommended guidelines (50 mg/kg/day and increased as needed by 50 mg/kg/day every 3 days up to a maximum dose of 150 mg/kg/day, divided BID).

Participants randomized to this arm will be treated with vigabatrin until 24 months of age or until they show evidence of clinical seizures or electrographic seizures on video EEG. If electrographic or clinical seizures occur while on vigabatrin, they will be eligible for Open label vigabatrin. Participants will be followed until 36 months of age.

ID	Term
D006222	Hamartoma
D009369	Neoplasms
D009378	Neoplasms, Multiple Primary
D009386	Neoplastic Syndromes, Hereditary
D065703	Malformations of Cortical Development, Group I
D054220	Malformations of Cortical Development
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020752	Neurocutaneous Syndromes
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins