Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 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.

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.

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.

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