Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. A 6-month Randomised, Double-blind, Placebo Controlled Multicentre Parallel Group Study to Evaluate Efficacy and Safety of Bumetanide 0.5mg Twice a Day Followed by an Open Label Active 6-month Treatment Period With Bumetanide (0.5mg Twice a Day) and a 6 Weeks Discontinuation Period After Treatment Stop.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 211
- 试验地点
- 50
- 主要终点
- Childhood Autism Rating Scale, Second Edition (CARS2) Total Raw Score
研究概览
简要总结
The purpose of this study was to evaluate the efficacity and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.
详细描述
The present study (CL3-95008-002) was performed in children from 2 to less than 7 years old presenting with ASD. A 6-month double-blind treatment period was performed in which efficacy and safety of bumetanide 0.5mg BID were assessed versus placebo. This double-blind period was followed by a 6-month open label treatment period of bumetanide 0.5mg twice daily in which long term safety was evaluated.
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
- 2 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients from 2 to less than 7
- •Primary diagnosis of ASD as per Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria
- •Criteria met for ASD on Autism Diagnostic Observation Schedule-Generic (ADOS-2) and Autism Diagnosis Interview Revised (ADI-R)
- •CGI (Clinical Global Impression) - Severity rating Score ≥ 4
- •Childhood Autism Rating Scale second edition (CARS2-ST or HF) total raw score ≥ 34
- •Social responsiveness Scale second edition (SRS-2) total score ≥ 66 T-Score
- •Absence of diagnosis of Fragile X or Rett Syndrome
- •Absence of any clinically significant abnormality likely to interfere with the conduct of the study according to the judgment of the investigator.
排除标准
- •Patients not able to follow the study assessments defined by the protocol, with the exception of self-rating questionnaires which will be assessed by parent/legal representative/caregiver for those patients unable to complete them
- •Patients having a high suicidal risk according to the investigator judgement
- •Chronic renal dysfunction
- •Chronic cardiac dysfunction
- •Patient with unstable psychotherapy, behavioural, cognitive or cognitive-behavioural therapy
- •Severe electrolyte imbalance that is likely to interfere with the study conduct or evaluation
研究组 & 干预措施
BUMETANIDE (S95008) followed by Open-Label S95008
Participants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
干预措施: Open-Label BUMETANIDE (S95008) for weeks 26 - 52 (Drug)
BUMETANIDE (S95008) followed by Open-Label S95008
Participants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
干预措施: BUMETANIDE (S95008) for week 0 - 26 (Drug)
PLACEBO followed by Open-Label S95008
Participants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
干预措施: PLACEBO for week 0 - 26 (Drug)
PLACEBO followed by Open-Label S95008
Participants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
干预措施: Open-Label BUMETANIDE (S95008) for weeks 26 - 52 (Drug)
结局指标
主要结局
Childhood Autism Rating Scale, Second Edition (CARS2) Total Raw Score
时间窗: Change from baseline to Week 26
The CARS2 total raw score range from 15 to 60. This scale is a behaviour rating scale intended to diagnose autism. A total score of 15 indicates that an individual behaviour is within normal limits, whereas a value of 60 indicates that the individual's behaviour is severly abnormal. In term of change from baseline, the greater the mean value decreases, the better it is.
次要结局
- Clinical Global Impression - Global Improvement (CGI-I) Score(At Week 26)
- Number of Patients With Abnormalities in 12-leads Electrocardiogram (ECG) Parameters(Week 26)
- Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE)(through week 52)
- Vineland Adaptative Behaviour Scale II (VABS II)(Change from baseline to Week 26)
- Acceptability and Palatability Questionnaires - Only Descriptive Analyses(Week 26)
- Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score(Change from baseline to Week 26)
- Columbia-Suicide Severity Scale Children's Version (C-SSRS-C)(Week 26)
- Paediatric Quality of Life Inventory (PedsQL) Questionnaire(Change from baseline to week 26)