Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
Childhood Absence Epilepsy, Petit Mal Epilepsy, Epilepsy
About this trial
This is an interventional treatment trial for Childhood Absence Epilepsy focused on measuring childhood absence epilepsy, CAE, petit mal epilepsy, epilepsy, seizures, ethosuximide, lamotrigine, valproic acid
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.
Sites / Locations
- The Children's Hospital of Alabama
- St. Joseph's Hospital and Medical Center
- Arkansas Children's Hospital
- University of California at San Diego
- Mattel Children's Hospital at UCLA
- Children's Hospital of Denver
- Yale University School of Medicine
- Children's National Medical Center
- Nemours Children's Clinic
- Miami Children's Hospital
- Children's Healthcare of Atlanta
- Children's Memorial Hospital
- Children's Hospital of Michigan
- Washington University in St. Louis
- Montefiore Medical Center
- Women and Children's Hospital of Buffalo
- NYU Comprehensive Epilepsy Center, Manhattan
- Cincinnati Children's Hospital
- Rainbow Babies & Children's Hospital
- Children's Hospital, Inc., PCTI
- Doernbecher Children's Hospital
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh
- LeBonheur Children's Medical Center
- Dallas Pediatric Neurology Associates
- Cook Children's Medical Center
- Texas Children's Hospital
- University of Utah/Primary Children's Medical Center
- Children's Hospital of The King's Daughter (Monarch Medical Research)
- Children's Hospital & Regional Medical Center
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Active Comparator
Active Comparator
Ethosuximide
Lamotrigine
Valproic acid
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)
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).
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)