Autism Spectrum Disorder (ASD)
Conditions
Brief summary
The purpose of this study was to evaluate the efficacy and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.
Detailed description
The present study (CL3-95008-001) was performed in children and adolescents from 7 to less than 18 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 BID in which long term safety was evaluated.
Interventions
DRUGBumetanide Oral Solution
Oral Solution dosed at 0.5mg/mL Taken twice daily
DRUGPlacebo
Oral Solution Taken twice daily
Sponsors
ADIR, a Servier Group company
Institut de Recherches Internationales Servier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients from 7 to less than 18 years * Out patients * 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 (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 total score (SRS-2 T-Score) ≥ 66 * Absence of known monogenic syndrome (Fragile X, Rett syndrome ...) * Absence of any clinically significant abnormality likely to interfere with the conduct of the study according to the judgment of the investigator
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Childhood Autism Rating Scale, Second Edition (CARS2) total raw score | Change from baseline to 6 month | Efficacy criterion The CARS2 is a 15 item rated instrument. The rating values given for the 15 areas are summed to produce a Total score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Global Improvement (CGI-I) score | At 6 months | Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient under study treatment |
| Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores | Change from baseline to 6 month | Efficacy criterion Scale designated to measure adaptative behaviour |
| Adverse events and Paediatric Adverse Event Rating Scale (PAERS) | On average of 52 weeks | Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation. |
| Abnormalities in 12-leads electrocardiogram (ECG) parameters | selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052 | Safety criterion |
| Social Responsiveness Scale, Second Edition (SRS-2) total raw score | Change from baseline to 6 month | Efficacy criterion 65 items scale measuring symptoms associated with autism |
| the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C) | Week000/Week012/Week026/Week038/Week052 | Scale which assesses suicidal ideation and suicidal behaviour |
| Tanner stage | Week000/Week026/Week052 | Safety criterion Assessment of Pubertal development |
| Acceptability and palatability questionnaire | Week026 | Acceptability and palatability criterion Assessment of the ease of use to use the dosing device |
| Paediatric Quality of Life Inventory (PedsQL) questionnaire | Week000/Week004/Week012/Week026/Week030/Week038/Week052 | Quality of Life criterion Assessment of parent/legal representative perception of patient health related quality of life |
| Renal ultrasound | selection visit/Week026/Week052 | Safety criterion Assessment of the renal function |
Countries
Brazil, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom
Outcome results
None listed