A Randomized, Double-Blind, Placebo-Controlled, Parallel Group 26-Week Dose-Investigating Study to Explore the Pharmacokinetics, Pharmacodynamic Effects, Efficacy, Safety and Tolerability of RO5186582 in Children With Down Syndrome Aged 6-11 Years
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 9
- 主要终点
- Anxiety, Depression, and Mood Scale (ADAMS) Score
研究概览
简要总结
This study will evaluate the safety, tolerability, efficacy, and pharmacokinetic and pharmacodynamic activity of 3 different dosages of RO5186582 compared with placebo. A total of approximately 46 participants will be enrolled, in order to have at least 32 evaluable, and will be randomly assigned to 1 of 4 treatments in a 1:1:1:1 ratio, with 9 children per treatment arm. The target ratio between 6-8 years and 9-11 years age groups is approximately 1:1 in each treatment arm, with a minimum of 3 children per age group in each treatment arm.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Down syndrome, except for mosaic Down syndrome
- •Available parent or caregiver to attend clinic visits and provide information about the participant's behavior and symptoms
排除标准
- •Any primary psychiatric comorbid disorder
- •History of infantile spasms, West syndrome, Lennox-Gastaut syndrome, early infantile epileptic encephalopathy, treatment-refractory epilepsy with cognitive/developmental regression, severe head trauma, or central nervous system (CNS) infection
- •Seizure event of any type within 12 months prior to Screening or relevant changes in anti-epileptic drugs 6 weeks prior to enrollment
- •Significant sleep disruption
- •Significant gastrointestinal, renal, hepatic, endocrine, or cardiovascular disease
- •New-onset or ongoing hematologic/oncologic disorder
- •Severe lactose intolerance
- •Participation in another clinical study within 1 month or 6 half-lives prior to first dose, or any extent of participation in Study BP29589 (NCT02451657)
研究组 & 干预措施
Placebo
Participants will receive matching placebo by mouth (PO) twice daily (BID) for up to 26 weeks.
干预措施: Placebo (Drug)
RO5186582 120 mg BID
Participants will receive RO5186582 at a dosage of 120 milligrams (mg) PO BID for up to 26 weeks.
干预措施: RO5186582 (Drug)
RO5186582 40 mg BID
Participants will receive RO5186582 at a dosage of 40 mg PO BID for up to 26 weeks.
干预措施: RO5186582 (Drug)
RO5186582 60 mg BID
Participants will receive RO5186582 at a dosage of 60 mg PO BID for up to 26 weeks.
干预措施: RO5186582 (Drug)
结局指标
主要结局
Anxiety, Depression, and Mood Scale (ADAMS) Score
时间窗: Baseline up to Week 6
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis
时间窗: Baseline up to Week 6
Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score
时间窗: Baseline up to Week 6
Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis
时间窗: Baseline up to Week 6
Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the Columbia Classification Algorithm for Suicide Assessment (C-CASA)
时间窗: Baseline up to Week 6
Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score
时间窗: Baseline up to Week 6
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score
时间窗: Baseline up to Week 6
Percentage of Participants With Adverse Events (AEs)
时间窗: Baseline up to Week 6
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis
时间窗: Baseline up to Week 6
次要结局
- Intellectual Quotient (IQ) as Assessed by the Leiter 3(Baseline up to Week 26)
- Sleep Disturbances as Assessed by the CSHQ Score(Baseline up to Week 26)
- Cognition as Assessed by the CMS Subtests Score(Baseline up to Week 26)
- Daily Functional Memory as Assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) Score(Baseline up to Week 26)
- Plasma Concentration of RO5186582(Predose (2 predose samples separated by at least 1 hour) at Weeks 2 and 6; and predose or postdose (as convenient) during Weeks 10, 17, and 26)
- Theta Power at Posterior Electrodes as Assessed Using EEG Analysis(Baseline up to Week 26)
- Clinical Global Impression-Improvement (CGI-I) Scale Score(Baseline up to Week 26)
- Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA(Baseline up to Week 26)
- Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score(Baseline up to Week 26)
- Adaptive Behavior as Assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) Score(Baseline up to Week 26)
- Percentage of Participants With AEs(Baseline up to Week 26)
- Percentage of Participants With Epileptiform Abnormalities as Assessed Using EEG Analysis(Baseline up to Week 26)
- ADAMS Score(Baseline up to Week 26)
- Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis(Baseline up to Week 26)