Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 31
- 主要终点
- Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy
研究概览
简要总结
The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.
详细描述
Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome that affects 10 to 15 percent of all children with epilepsy. Individuals with CAE have brief staring spell seizures that occur suddenly, unpredictably, and frequently throughout the day. These seizures impair the children's ability to learn and play, and lead to higher injury rates.
There are many medications used to treat seizures, but only 3 generally are used as the first treatment for children with CAE: ethosuximide, lamotrigine, and valproic acid. The goal of this study is to determine which of these 3 medicines is the best first choice as treatment for children with CAE.
Approximately 439 children, recruited over a 3-year period at 32 medical centers in the US, will take part in this 5-year study. Participants will be randomly given one of the 3 common CAE treatments-ethosuximide, lamotrigine, or valproic acid-and will make regular visits to a clinic every 1 to 3 months for approximately 2 years. During the visits, participants will undergo regular testing to determine if the medicine is working, to watch for side effects, and to help researchers learn more about the responses to these medicines. In addition, researchers hope to develop methods that may be used in the future to help choose the best medicine for each individual diagnosed with CAE.
Also included in the study will be pharmacokinetics and pharmacogenetics research. Pharmacokinetics is the study of how the body absorbs, distributes, metabolizes, and excretes drugs. Pharmacogenetics is the study of genetic determinants of the response to drugs. Knowledge gained from this study may lead to individualized treatment for children with CAE, and may also be beneficial for other pediatric and adult seizure disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 30 Months 至 13 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
- •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/mm
- •Platelets >/= (greater than or equal to) 120, 000 /mm
- •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).
排除标准
- •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.
研究组 & 干预措施
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)
干预措施: Ethosuximide (Drug)
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).
干预措施: Lamotrigine (Drug)
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)
干预措施: Valproic acid (Drug)
结局指标
主要结局
Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy
时间窗: First 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.
次要结局
- Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT(First 16-20 weeks of double blind therapy)
- Number of Participants With Freedom From Treatment Failure at 12 Months of Double Blind Therapy(First 12 months of double blind therapy)