An Open-Label Study of the Safety and Tolerability of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 906
- 试验地点
- 118
- 主要终点
- Number of Confirmed Social Responsiveness Scale (SRS) Responders
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of memantine in pediatric (6-12 years old) patients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and to identify responders for participation in a follow-up randomized withdrawal study.
详细描述
This 50-week multicenter and multinational clinical study is comprised of a 2-week screening period, a 6-week open-label dose-titration period followed by a variable duration maintenance period (up to 42 weeks).
Patients with at least 12 weeks of investigational product exposure who meet the protocol specified responder criterion at two consecutive visits separated by at least two weeks are eligible to transition to a randomized withdrawal study. A responder is defined as a patient who demonstrates at least a 10 point improvement (reduction in score) in the Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 total raw score.
Weight based dose limits were selected in this study to ensure that exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng·h/mL which represents a 10-fold lower exposure than observed at the No observed adverse effect level (NOAEL) of 15 mg/kg/day in juvenile rats.
The weight-based dose limits in this study were as follows:
- Group A: ≥ 60 kg; maximum 15 mg/day
- Group B: 40-59 kg; maximum 9 mg/day
- Group C: 20-39 kg; maximum 6 mg/day
- Group D: < 20 kg; maximum 3 mg/day
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female outpatients.
- •Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
- •Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study
排除标准
- •Have enrolled in Study MEM-MD-57A
- •Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well-being.
- •Participation in any other clinical investigation using an experimental drug within 30 days of screening.
- •Having any primary psychiatric (Axis I) diagnosis other than autism, Asperger's Disorder, and PDD-NOS.
- •Meeting DSM-IV-TR criteria for bipolar I disorder, psychotic disorder not otherwise specified, posttraumatic stress disorder, schizophrenia, or major depressive disorder within the past 6 months
研究组 & 干预措施
Memantine Hydrochloride (HCl)
Once daily oral administration of open-label memantine for up to 48 weeks: 6-week dose-titration period followed by up to 42-week maintenance period.
干预措施: Memantine Hydrochloride (HCl) (Drug)
结局指标
主要结局
Number of Confirmed Social Responsiveness Scale (SRS) Responders
时间窗: Visit 1 (Baseline) to Visit 8 (week 48/Final Visit)
A confirmed SRS responder was defined as a patient who had at least 12 weeks of exposure to memantine, and a ≥ 10-point reduction in the SRS total raw score relative to baseline at 2 consecutive visits separated by at least 2 weeks. The SRS is a 65-item, caregiver-rated assessment scale that measures observable items on social behavior and social language use, as well as characteristics of autism in a naturalistic social setting. Each item is rated on a scale from 0 (never true) to 3 (almost always true). The SRS total raw score ranges from 0 to 195; a higher score indicates greater severity of social impairment.
次要结局
未报告次要终点