An Open-label (Part One) and a Randomized, Double-blind, Placebo-Controlled (Part Two) Study of the Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Pediatric Patients With Autism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 2
- 主要终点
- Extent of Absorption of Memantine (Part One)
研究概览
简要总结
The purpose of this study is to investigate the safety and efficacy of memantine extended release, as well as its extent of absorption in pediatric patients with autism.
详细描述
This is a multicenter, two-part study in pediatric (ages 6 to 18 years) patients diagnosed with autism.
Patients participating in Part One will receive a single open-label dose of memantine. Blood samples for pharmacokinetic analysis will be collected.
Part Two is a randomized, double-blind, placebo-controlled 12-week efficacy and safety study evaluating change in all core domains (social interactions, communication, and restricted interests and repetitive behaviors) of autism.
In the Forest autism trials conducted in children ages 6-12, dosing with an extended release formulation of memantine was weight-based. These weight based dose limits were selected to ensure exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng∙h/mL that represented a 10-fold lower exposure than observed at the NOAEL (No observed adverse effect level) of 15 mg/kg/day in juvenile rats.
The weight-based dose limits in these studies were as follows:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females ages 6 to 12 years
- •Diagnosis of autistic disorder, according to DSM-IV-TR using Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule (modules 2 & 3).
- •A knowledgeable caregiver capable of providing reliable information about the patient's condition, able to attend all clinic visits with the patient
- •Patients over age 12, only if they completed Study MEM-PK-21
排除标准
- •Medical history of active epilepsy/seizure disorder except simple febrile seizures
- •Participation in any other clinical investigation using an experimental drug within 30 days of the start of this study
研究组 & 干预措施
1
Once daily oral administration of memantine for 12 weeks.
干预措施: Memantine - Extended Release (ER) (Drug)
2
Once daily oral administration of placebo for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Extent of Absorption of Memantine (Part One)
时间窗: Baseline to 144 hours. Measurements were taken 0 (predose), 4, 8, 24, 30, 48, 96 and 144 hours post-dose
Area under the plasma concentration vs. time curve (AUC) for memantine, as measured in units of nanogram x hours per milliliter.
Change in Total Raw Score of Social Responsiveness Scale
时间窗: From Baseline to Week 12
The Social Responsiveness Scale (SRS) is a 65-item informant-rated assessment, ranging from 0 (no impairment) to 195 (severe social impairment). Each item is associated with 1 of 5 subscales (social awareness, social cognition, social communication, social motivation and autistic mannerisms). Each item is rated on a 4-point scale from 1 (not true) to 4 (almost always true). The scores are then transposed to a scale from 0 to 3 and scores are summed within each of the 5 subscales. A higher score indicates greater severity of social impairment.
次要结局
- Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale(From Baseline to Week 12)
- Core Autism Treatment Scale-Improvement: Total Score(At Week 12)
- Core Autism Treatment Scale-Improvement: Social Interaction(At Week 12)
- Core Autism Treatment Scale-Improvement: Communication(At Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale(From Baseline to Week 12)
- Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale(From Baseline to Week 12)