Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study | NCT00088452

ID	Type	Description	Link
U01NS045803	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
Ethosuximide	Active Comparator	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower)	Drug: Ethosuximide
Lamotrigine	Active Comparator	Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower).	Drug: Lamotrigine
Valproic acid	Active Comparator	Valproic acid Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight): 250mg Depakote capsules OR 125mg Depakote sprinkles. Dosing: Depakote was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 3000 mg/day (whichever was lower)

Name	Type	Description	Arm Group Labels	Other Names
Ethosuximide	Drug	Ethosuximide is a common treatment for childhood absence epilepsy.	Ethosuximide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy	Treatment failure was defined as persistence of absence seizures at week 16 or week 20, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, a moderately severe rash (possibly drug-related), pancreatitis, or increase in the body-mass index of at least 3.0 from baseline, dose-limiting toxicity after a single downward dose modification, or withdrawal initiated by the parent or physician.	First 16-20 weeks of double blind therapy

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT	A Confidence Index of 0.60 or higher on the Conners' Continuous Performance Test at the visit at 16 or 20 weeks or at an earlier visit when treatment was discontinued (as long as the discontinuation occurred 1 month or more after the baseline visit and was not due to intolerable adverse events). A Confidence Index of 0.60 corresponds to a 60% probability that the child has clinical attention deficit disorder.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis: Clinical diagnosis of Childhood Absence Epilepsy consistent with the International League against Epilepsy Proposal for Revised Classification of Epilepsies and Epileptic Syndromes (3).
EEG: Interictal EEG demonstrating bilateral synchronous symmetrical approximate 3 Hz spike waves on a normal background with at least one burst lasting >/= (greater than or equal to) 3 seconds.
Age > 2.5 years and < 13 years of age at study entry.
Body weight >/= (greater than or equal to) 10 kilograms.
Body Mass Index: BMI for age =/< 99th percentile (based on the CDC BMI for age growth curves for boys/girls [http://www.cdc.gov/growthcharts\], Appendix 1).
Hepatic:
AST/ALT < 2.5 times the upper limit of normal
Total bilirubin < 1.5 times the upper limit of normal.
Hematologic:
Absolute neutrophil count >/= (greater than or equal to) 1500/mm3.
Platelets >/= (greater than or equal to) 120, 000 /mm3.
Female subjects must be premenarchal at the time of enrollment and must be willing to practice abstinence for the duration of the study.
Parent/legal guardian(s) willing to sign an IRB approved informed consent.
Subject assent (when appropriate and as dictated by local IRB).

Exclusion Criteria:

Treatment for CAE with anti-seizure medications (AED) for a period of greater than 7 days prior to randomization.
History of a major psychiatric disease (e.g., psychosis, major depression).
History of autism or pervasive development disorder.
History of non-febrile seizures other than typical absence seizures. This includes a history of an afebrile generalized tonic clonic seizure.
Clinical signs and symptoms consistent with a diagnosis of juvenile absence epilepsy or juvenile myoclonic epilepsy as delineated by the International League against Epilepsy Proposal for Revised Classification of Epilepsies and Epileptic Syndromes (3).
History of recent or present significant or medical disease, i.e., cardiovascular, hepatic, renal, gynecologic, musculoskeletal, metabolic, or endocrine.
History of a severe dermatologic reaction (e.g., Stevens Johnson, toxic epidermolysis necrosis) to medication.
Subject or parent/legal guardian might not be reasonably expected to be compliant with or to complete the study.
Participation in a trial of an investigational drug or device within 30 days prior to screening.
Use of systemic contraceptive for any indication, including acne.

Name	Affiliation	Role
Tracy A. Glauser, MD	Children's Hospital Medical Center, Cincinnati	Principal Investigator
Peter Adamson, MD	Children's Hospital of Philadelphia	Principal Investigator
Avital Cnaan, PhD	Children's National Research Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The Children's Hospital of Alabama		Birmingham	Alabama	35233	United States
St. Joseph's Hospital and Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23167925	Background	Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Adamson PC; Childhood Absence Epilepsy Study Team. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013 Jan;54(1):141-55. doi: 10.1111/epi.12028. Epub 2012 Nov 21.
27986874	Background	Cnaan A, Shinnar S, Arya R, Adamson PC, Clark PO, Dlugos D, Hirtz DG, Masur D, Glauser TA; Childhood Absence Epilepsy Study Group. Second monotherapy in childhood absence epilepsy. Neurology. 2017 Jan 10;88(2):182-190. doi: 10.1212/WNL.0000000000003480. Epub 2016 Dec 16.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.

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
ICF	No	No	Yes	Informed Consent Form	Aug 18, 2005	Aug 13, 2020

Arm/Group Information

ID	Title	Description
BG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.
BG001	Lamotrigine	Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower). Lamotrigine: Lamotrigine is a common treatment for childhood absence epilepsy.
BG002	Valproic Acid	Valproic acid Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight): 250mg Depakote capsules OR 125mg Depakote sprinkles. Dosing: Depakote was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 3000 mg/day (whichever was lower) Valproic acid: Valproic acid is a common treatment for childhood absence epilepsy.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG000155 BG001149 BG002147 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00090 BG00192 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000155 BG001149 BG002

BMI > 90th percentile for age

BMI > 90th percentile for age using the units of kg/m2

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00043 BG00144 BG002

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

Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy

Treatment failure was defined as persistence of absence seizures at week 16 or week 20, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, a moderately severe rash (possibly drug-related), pancreatitis, or increase in the body-mass index of at least 3.0 from baseline, dose-limiting toxicity after a single downward dose modification, or withdrawal initiated by the parent or physician.

Posted

Count of Participants

Participants

First 16-20 weeks of double blind therapy

ID	Title	Description
OG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.
OG001	Lamotrigine	Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower). Lamotrigine: Lamotrigine is a common treatment for childhood absence epilepsy.
OG002	Valproic Acid	Valproic acid Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight): 250mg Depakote capsules OR 125mg Depakote sprinkles. Dosing: Depakote was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 3000 mg/day (whichever was lower) Valproic acid: Valproic acid is a common treatment for childhood absence epilepsy.

Units	Counts
Participants	OG000154 OG001146 OG002146

Title

Denominators

Categories

Title	Measurements
	OG00081 OG00143 OG00285

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	Calculations of sample size were based on the ability to detect a 20% difference in freedom-from failure rates (three pairwise comparisons) at 16 weeks with 80% power at a two-sided P value of 0.017 and one interim analysis. Sample size of 398 was increased to 446 subjects to account for two stratification factors and a 5% dropout rate; this sample size allowed the detection of a difference of 0.5 SD in the Confidence Index on the Conners' Continuous Performance Test with a power exceeding 80%.	Chi-squared		<0.001		Odds Ratio (OR)	2.66			2-Sided	95	1.65	4.28			odds ratio with ethosuximide vs. lamotrigine

Secondary

Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT

A Confidence Index of 0.60 or higher on the Conners' Continuous Performance Test at the visit at 16 or 20 weeks or at an earlier visit when treatment was discontinued (as long as the discontinuation occurred 1 month or more after the baseline visit and was not due to intolerable adverse events). A Confidence Index of 0.60 corresponds to a 60% probability that the child has clinical attention deficit disorder.

Those subject who took the Conners' Continuous Performance Test at the visit at 16 or 20 weeks or at an earlier visit when treatment was discontinued (as long as the discontinuation occurred 1 month or more after the baseline visit and was not due to intolerable adverse events).

Posted

Count of Participants

Participants

First 16-20 weeks of double blind therapy

ID	Title	Description
OG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.

Secondary

Number of Participants With Freedom From Treatment Failure at 12 Months of Double Blind Therapy

Treatment failure was defined as persistence of absence seizures at 12 months of double blind therapy, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, a moderately severe rash (possibly drug-related), pancreatitis, or increase in the body-mass index of at least 3.0 from baseline, dose-limiting toxicity after a single downward dose modification, or withdrawal initiated by the parent or physician.

Posted

Count of Participants

Participants

First 12 months of double blind therapy

ID	Title	Description
OG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.
OG001	Lamotrigine	Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower). Lamotrigine: Lamotrigine is a common treatment for childhood absence epilepsy.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ethosuximide	Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower) Ethosuximide: Ethosuximide is a common treatment for childhood absence epilepsy.	155	4	155	103	155
EG001	Lamotrigine	Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower). Lamotrigine: Lamotrigine is a common treatment for childhood absence epilepsy.	149	2	149	78	149
EG002	Valproic Acid	Valproic acid Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight): 250mg Depakote capsules OR 125mg Depakote sprinkles. Dosing: Depakote was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 3000 mg/day (whichever was lower) Valproic acid: Valproic acid is a common treatment for childhood absence epilepsy.	147	2	147	100	147

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Generalized tonic clonic seizure	Nervous system disorders	Systematic Assessment		EG0002 events2 affected155 at risk EG0010 events0 affected149 at risk EG0021 events1 affected147 at risk
Enteritis	Infections and infestations	Systematic Assessment	Due to Salmonella poisoning	EG0000 events0 affected155 at risk EG0011 events1 affected149 at risk EG0020 events0 affected147 at risk
Prolonged Absence Seizure	Nervous system disorders	Systematic Assessment		EG0000 events0 affected155 at risk EG0011 events1 affected149 at risk EG0020 events0 affected147 at risk
Pneumonia, diarrhea, vomiting	Nervous system disorders	Systematic Assessment		EG0001 events1 affected155 at risk EG0010 events0 affected149 at risk EG0020 events0 affected147 at risk
Non-epileptic movements	Psychiatric disorders	Systematic Assessment		EG0001 events1 affected155 at risk EG0010 events0 affected149 at risk EG0020 events0 affected147 at risk
Acting Out	Psychiatric disorders	Systematic Assessment	Voluntarily committed	EG0000 events0 affected155 at risk EG0010 events0 affected149 at risk EG0021 events1 affected147 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Fatigue	General disorders	Systematic Assessment	EG00015 events15 affected155 at risk EG00113 events13 affected149 at risk EG00218 events18 affected147 at risk
Headache	General disorders	Systematic Assessment	EG00019 events19 affected155 at risk EG00112 events12 affected149 at risk EG00212 events12 affected147 at risk
Sleep problem	General disorders	Systematic Assessment	EG00010 events10 affected155 at risk EG0015 events5 affected149 at risk EG00214 events14 affected147 at risk
Nausea, vomiting, or both	Gastrointestinal disorders	Systematic Assessment	EG00023 events23 affected155 at risk EG0012 events2 affected149 at risk EG00210 events10 affected147 at risk
Stomach upset	Gastrointestinal disorders	Systematic Assessment	EG00016 events16 affected155 at risk EG0014 events4 affected149 at risk EG0028 events8 affected147 at risk
Increased appetite	Gastrointestinal disorders	Systematic Assessment	EG0005 events5 affected155 at risk EG0017 events7 affected149 at risk EG00213 events13 affected147 at risk
Decreased appetite	Gastrointestinal disorders	Systematic Assessment	EG0008 events8 affected155 at risk EG0015 events5 affected149 at risk EG0023 events3 affected147 at risk
Weight increase	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected155 at risk EG0013 events3 affected149 at risk EG00210 events10 affected147 at risk
Hyperactivity	Psychiatric disorders	Systematic Assessment	EG00014 events14 affected155 at risk EG00110 events10 affected149 at risk EG00215 events15 affected147 at risk
Hostility	Psychiatric disorders	Systematic Assessment	EG0004 events4 affected155 at risk EG00110 events10 affected149 at risk EG00218 events18 affected147 at risk
Personality change	Psychiatric disorders	Systematic Assessment	EG0004 events4 affected155 at risk EG0019 events9 affected149 at risk EG00216 events16 affected147 at risk
Decrease in concentration	Nervous system disorders	Systematic Assessment	EG0006 events6 affected155 at risk EG0015 events5 affected149 at risk EG00211 events11 affected147 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG00014 events14 affected155 at risk EG0013 events3 affected149 at risk EG0024 events4 affected147 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0004 events4 affected155 at risk EG0018 events8 affected149 at risk EG0028 events8 affected147 at risk
Attentional difficulties	Nervous system disorders	Systematic Assessment	EG0003 events3 affected155 at risk EG0015 events5 affected149 at risk EG00210 events10 affected147 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0009 events9 affected155 at risk EG0014 events4 affected149 at risk EG0022 events2 affected147 at risk
Memory problems	Nervous system disorders	Systematic Assessment	EG0000 events0 affected155 at risk EG0014 events4 affected149 at risk EG0028 events8 affected147 at risk

ID	Term
D004832	Epilepsy, Absence
D004827	Epilepsy
D012640	Seizures

ID	Term
D004829	Epilepsy, Generalized
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D000073376	Epileptic Syndromes
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013388	Succinimides
D007094	Imides
D009930	Organic Chemicals
D011760	Pyrrolidinones
D011759	Pyrrolidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014227	Triazines
D010421	Pentanoic Acids
D014631	Valerates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005232	Fatty Acids, Volatile
D005227	Fatty Acids
D008055	Lipids

ID	Term
D005013	Ethosuximide
D000077213	Lamotrigine
D014635	Valproic Acid